The Effect of Thylakoid Membranes of Spinach Extract Supplementation on Atherogenic, Glycemic, and Anthropometric Indices and Renal Function in Obese PCOS Women under a Hypo-Caloric Diet: A Randomized, Double-Blind, Controlled Trial

Nikrad, Negin; Mokhtari Ardekani, Abnoos; Farhangi, Mahdieh Abbasalizad; Zahiri Tousi, Ayda; Pourteymour Fard Tabrizi, Fatemeh; Vaezi, Maryam; Hemmati, Salar

doi:https://doi.org/10.1155/2023/9408072

Journal of Food Biochemistry

On this page

Abstract Introduction Methods Discussion Conclusion Data Availability Additional Points Disclosure Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2023 | Article ID 9408072 | https://doi.org/10.1155/2023/9408072

The Effect of Thylakoid Membranes of Spinach Extract Supplementation on Atherogenic, Glycemic, and Anthropometric Indices and Renal Function in Obese PCOS Women under a Hypo-Caloric Diet: A Randomized, Double-Blind, Controlled Trial

Negin Nikrad,¹Abnoos Mokhtari Ardekani,²Mahdieh Abbasalizad Farhangi,³Ayda Zahiri Tousi,⁴Fatemeh Pourteymour Fard Tabrizi,⁵Maryam Vaezi,^6,7and Salar Hemmati³

Academic Editor: Anandakumar Pandi

Received03 Aug 2023

Revised22 Sept 2023

Accepted06 Oct 2023

Published16 Oct 2023

Abstract

Background. Hyperandrogenism is a common disorder in women with polycystic ovary syndrome (PCOS) that can cause changes in body fat distribution and the amount of visceral adipose tissue. Visceral adiposity impairs insulin action, leading to insulin resistance (IR), cardiovascular disease, and renal disorders due to obesity and insulin resistance. Dietary thylakoids reduce visceral fat mass by suppressing appetite and regulating body weight. The present trial aimed to evaluate the fat distribution and renal function after thylakoid membranes of spinach supplementation along with a hypo-caloric diet. Methods. Forty-four obese women with PCOS participated in this randomized, double-blind, placebo-controlled clinical trial for 12 weeks and were allocated to receive 5 gr of thylakoid membranes of spinach extract combined with hypo-caloric diet or 5 gr placebo along with a hypo-caloric diet. Novel atherogenic and anthropometric indices including the atherogenic index of plasma (AIP), Castelli risk index I (CRI-I), Castelli risk index II (CRI-II), TyG-BMI (TyG-BMI), metabolic score for insulin resistance (METS-IR), abdominal volume index (AVI), body adiposity index (BAI), a body shape index (ABSI), and serum urea, creatinine, and total protein were assessed at the baseline and end of the intervention period. Results. Thylakoid membranes of spinach supplementation along with a calorie restriction diet showed a significant decrease in the AIP, CRI-I, II, TyG-BMI, and METS-IR ( < 0.05). AVI, BAI, and ABSI were found to reduce in the thylakoid and placebo groups ( < 0.05). However, the changes in serum urea, creatinine, and total protein did not show significant differences between the intervention and placebo groups. Conclusion. After 12-week supplementation with thylakoid membranes extracted from spinach, improvements in the value of atherogenic indices and insulin resistance surrogate markers were observed, while this intervention did not make a significant difference in the serum levels of renal function factors. This trial is registered with IRCT20140907019082N9.

1. Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects 5–10% of women during their reproductive age [1]. PCOS is defined as chronic anovulation (often shown as oligo—or amenorrhea), metabolic abnormalities (insulin resistance (IR), hyperinsulinemia, obesity, and acanthosis nigricans), and hyperandrogenism [2]. PCOS is a heterogeneous disease that is not only associated with long-term metabolic abnormalities such as IR but also associated with endothelial dysfunction, dyslipidemia, and systemic inflammation which exposes individuals to a higher risk of cardiovascular disease (CVD) [3] and kidney diseases due to obesity and IR, which have multiple links with kidney diseases [4]. Comorbidities of PCOS include traditional CVD risk factors such as obesity, impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), dyslipidemia, and hypertension [5, 6].

Women with PCOS who have hypertension are very susceptible to kidney disorders [7]. Furthermore, high levels of androgens in PCOS individuals contribute to renal impairment by increasing blood pressure and affecting renal function [8] as well as alterations in body fat distribution [9]. Previous research has found an association between androgen levels and visceral adipose tissue (VAT) and the amount of abdominal fat [10–12]. According to studies on fat compartmentalization in PCOS, women with PCOS show a predisposition to abdominal fat distribution when anthropometric measurements are performed [13]. It has been discovered that visceral obesity causes metabolic and endocrine abnormalities that are critical in the pathogenesis of PCOS [14–16]. Visceral obesity also affects the action of insulin, resulting in IR and compensatory systemic hyperinsulinism and hyperandrogenism development [17, 18], as well as being associated with elevated adipocytokine production, proinflammatory activity, a reduction in insulin sensitivity, a greater risk of developing T2DM, high triglyceride (TG), low-HDL cholesterol, dyslipidemia, atherosclerosis, hypertension, and an increased mortality rate [17]. Body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHTR) can all be used to evaluate central obesity in PCOS patients, although some studies have indicated that these indices provide limited data on fat distribution. Consequently, more appropriate anthropometric indices that incorporate body shape with disease prediction in order to assess central obesity are required; novel anthropometric indices can represent central obesity more accurately than traditional anthropometric indices [19]. Abdominal volume index (AVI) is a reliable anthropometric measure for estimating obesity that is strongly related to IGT and T2DM [20] and predicting metabolic abnormalities [21]. Body adiposity index (BAI) is a valuable measurement for predicting glucose metabolism problems [22]. A body shape index (ABSI) was found to be more closely related to the risk of T2DM than BMI [23]. Therefore, it is critical to quantitatively study body fat deposition changes in PCOS through novel anthropometric indices to evaluate the fat distribution and investigate the visceral adiposity independent of the overall obesity of women with PCOS.

Thylakoids are chloroplast inner photosynthesis membrane structures that could be isolated from green plants such as spinach [24]. Thylakoids are made up of protein-bound pigments like chlorophyll, beta-carotene, lutein, and zeaxanthin, as well as antioxidants including carotenoids and vitamin E [25, 26].

Dietary thylakoid membranes bind to pancreatic lipase and colipase, reducing fat digestion in the intestine, decreasing food consumption, as well as diminishing visceral fat mass [27]. In animal studies [28, 29], when the diet was supplemented with spinach extract containing thylakoids, a significant reduction in body weight and body fat percentage was observed. Montelius et al. [30] demonstrated that while green plant membranes were added to the daily diet for three months, they significantly decreased body weight, total cholesterol, and low-density lipoprotein cholesterol levels in overweight women compared to a control group. Meanwhile, thylakoids were shown to promote body weight loss significantly in addition to anthropometric indices including BMI, WC, WHR, and FM, which significantly decreased in 12 weeks of intervention [31, 32].

Moreover, spinach extract, the richest source of nitrate, has been shown to have cardioprotective benefits by increasing postprandial plasma nitrate and nitrite concentrations [33] and lowering blood pressure. Furthermore, it could have antihypertensive actions by regulating body weight and insulin resistance [34, 35]. Based on observational research, hypertension has long been considered a risk factor for kidney function impairment [36, 37]. Furthermore, extensive epidemiological studies have shown that obesity, particularly visceral obesity, plays a critical role in the development of chronic renal disease [38]. Therefore, we hypothesize that thylakoid supplements along with a low-calorie diet can have beneficial effects on the distribution of visceral fat, in addition to improving glycemic, lipid, and anthropometric indices and renal function in obese PCOS women.

2. Methods

2.1. Trial Design and Participants

The present study was a randomized, double-blind, placebo-controlled clinical trial, conducted in the northwest of Iran, Tabriz city. A random sample of individuals with obesity and diagnosed PCOS were recruited from Sheykholrayis Polyclinic and the gynecology and infertility clinics of AL Zahra Hospital (Tabriz, Iran). PCOS was diagnosed based on the Rotterdam criteria, which was diagnosed with two of the following three criteria: hyperandrogenism, ovulation disorder, and polycystic ovary. Eligibility criteria required individuals aged 20–45 years old to have received only oral contraceptive pills (OCPs) as routine medical therapy if there was no evidence of thyroid disorders, adrenal cortex dysfunction, or hyperprolactinemia. The exclusion criteria of subjects were as follows: menopause, or pregnancy, or lactation; being a smoker or a passive smoker; any other endocrine disorder; or cardiovascular disease; taking supplements or drugs affecting appetite and weight, insulin sensitivity, or ovulation induction; having any special diet before starting the study and/or undergoing special physical activity training. Forty-eight obese PCOS patients were recruited for this study, and the study’s aim was explained to all participants before data gathering. All patients provided written informed consent after receiving a thorough description of the research protocols.

The current trial was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the research vice chancellor of Tabriz University of Medical Sciences, Tabriz, Iran (IRCT registration number: IRCT20140907019082N9 and ethics code: IR.TBZMED.REC.1401.892).

2.2. Study Protocol

Using random assignment software (RAS) and the randomized block method, an allocation sequence was generated, and participants were randomized into two groups with equal sample sizes (1 : 1). To perform allocation concealment, sequentially numbered opaque sealed envelopes are used. The envelopes are opened sequentially at the beginning of the intervention in the order of entry, and the grouping of participants is determined according to the envelope containing the allocation plan inside it. The personnel involved in the fieldwork and participants were kept concealed regarding the randomization during the whole study. The researchers and patients were kept concealed about the randomization and distribution until the final analyses were performed.

2.3. Interventions

The eligible individuals were randomly recruited to receive 5 gr/day thylakoid extract powder or 5 g/day placebo (raw corn starch powder) for 12 weeks along with a low-calorie diet (500 kilocalories less than the estimated daily energy requirement for each participant) prescribed by an expert dietitian for both groups. This trial was conducted under double-blind conditions; the intervention, randomization, and allocation were administered by an independent person who was not involved in any clinical procedures of the study; both study personnel and participants were blinded regarding the allocation and treatment until the end of the analysis. To ensure the blinding process, placebo sachets (corn starch) were colored with an edible green color. Both placebo and thylakoid powders were flavored with kiwi fruit so that the two types of sachets were completely identical in all visual, olfactory, and textural aspects. The participants were instructed to dissolve the sachet of powder content in a glass of water and consume it 30 minutes before lunch. Adherence to the recommended hypo-caloric diet was assessed using dietary intake records for 3 days (2 weekdays and 1 weekend) at the beginning of the study, the sixth week, and at the end of the study.

2.4. Outcomes

The primary study outcome was to evaluate and compare the value of novel glycemic, atherogenicity, and anthropometric indices among PCOS patients at the baseline and end of 12 weeks of thylakoid supplementation along with a low-calorie diet in two groups: intervention and placebo. Secondary outcome measures were the comparison of renal function markers, including urea, creatinine, albumin, and total protein, in two groups at the beginning and end of the study. For routine blood measurement and any anthropometric measurements, the participants were present between 8:00 and 10:00 am, following the fasting state in the designated place in the presence of staff who were professional healthcare providers. Detailed measurements of each index and biochemical factor are given below.

2.5. Anthropometric and Body Composition Measurements

The height and weight of the participants were measured using a wall-mounted stadiometer and a Seca scale (Seca co., Hamburg, Germany) to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference was measured at the midpoint between the lower costal margin and the iliac crest using a tape measure to the nearest 0.1 cm. Hip circumference was measured over the widest part of the buttocks and was recorded to the nearest 0.1 cm. Body composition was assessed using the Tanita MC-780 SMA (Amsterdam, the Netherlands), a validated instrument for bioelectrical impedance analysis (BIA).

2.6. Atherogenicity, Insulin Resistance, and Anthropometric Indices

The formulas that were implemented to calculate the indices measured in the present study are indicated below [19, 39, 40], and the optimal cut off values were also obtained from previous studies [41–46]:

2.7. Laboratory Analysis

At the study baseline and after the intervention period, venous blood samples (approximately 10 ml) were obtained following a minimum of 12 h overnight fasting and resting in bed during the early follicular phase of the menstrual cycle (days 2–5). The collected blood samples were immediately centrifuged, and the serum samples were separated from the whole blood and frozen at −80 °C until the time of measurement. Serum FBG (glucose oxidase, phenol, 4-amino antipyrine peroxidase method, Pars Azmoon, Cat No: 1500017, Karaj, Iran. Intra- and interassay coefficients of variation (CV) were 1.63 and 2.2, respectively), TG (glycerol-3-phosphate oxidase phenol 4-aminoantipyrine peroxidase method, Pars Azmoon, Cat No: 1500032, Karaj, Iran; Intra- and interassay CVs were 1.7 and 1.58, respectively), TC (cholesterol oxidase Phenol 4-aminoantipyrine peroxidase method, Pars Azmoon, Cat No: 1500010, Karaj, Iran; Intra- and interassay CVs were 1.6 and 2, respectively), and HDL-C analyzed are through enzymatic methods using the colorimetric technique by commercial kits (Man company, Cat No: 613066, Iran. Intra- and interassay CVs were 1.16 and 0.98) by an auto-analyzer (Hitachi-917, Tokyo, Japan). Also, the Friedewald equation was used to calculate LDL-C [47]. The serum insulin level was measured by using an ELISA kit (Insulin kit, Monobind, Lake Forest, Cat No: 2425300, USA. Intra- and interassay CVs were <5.6% both). Blood creatinine (Man company, Cat No.: 613027, Iran. Intra- and interassay CVs were <3.5% both), urea (Man company, Cat No: 613020, Iran. Intra- and interassay CVs were 1.1 and 1.4, respectively), albumin (Man company, Cat No: 613040, Iran Intra- and interassay CVs were 2 and 1.8, respectively), and total protein (Bioassay Technology Laboratory, Shanghai Korean Biotech, Shanghai City, Cat No: E1149Hu, China. Intra- and interassay coefficients of variation (CV) were 1.5 and 2.6, respectively) were measured using the commercial kits. Hormonal profiles including LH, FSH, and total testosterone were determined using ELISA kits (Bioassay Technology Laboratory, Shanghai Korean Biotech, Shanghai City, China. Cat No: E1037Hu, E1001Hu, and E1036H, respectively. Intra-and interassay CVs were less than 5.0% for these measurements), according to the manufacturer’s instructions.

2.8. Statistical Analysis

Sample size calculation was performed using sample size software (PASS; NCSS, LLC, US, version 15), taking into consideration the mean ± standard deviation results for FBG from the study conducted by Montelius et al. [48] with a 95% confidence interval and a power of 90% in two-sided tests. Considering the drop-out rate of 15%, the final sample size of 24 participants within each group (48 in total) was estimated. All analyses were done using SPSS version 23 (SPSS Inc., Chicago, IL, USA). Results with values below 0.05 were considered statistically significant. The Kolmogorov–Smirnov test was performed to examine the normality of the data distribution. The distribution of data was presented as the mean ± SD for quantitative data with normal distribution, and frequency (%) for qualitative data. The independent t-test was used to compare qualitative data between the two groups at the baseline and after the intervention. Qualitative data were compared with the chi-square test. A comparison of the two groups after 12 weeks of intervention of the study was performed by the analysis of covariance (ANCOVA) after adjusting for the baseline values and potential confounders including baseline values of each variable, age, and physical activity and total calorie intake. Also, one-way ANCOVA was used to estimate the effect size by taking the difference in the means of the two groups and dividing it by the pooled standard deviation. Independent t-tests are used for reporting the mean difference (MD) with a 95% confidence interval (CI) for between-group differences.

3. Result

Forty-eight eligible women diagnosed with PCOS with obesity who matched the selection criteria were recruited for this study and randomized to placebo and intervention groups (n = 24 in each group). Three participants from the thylakoid group (due to in vitro fertilization therapy and loss of follow-up) and one subject from the placebo group (due to travel) fell out of the research. Consequently, forty-four participants remained during the 12-week intervention period (intervention (n = 21) and placebo (n = 23)) (Figure 1). During the study, no adverse effects or signs were recorded after the participants consumed thylakoid powder, so no interim analysis and stopping instructions were done in the process of the present study.

The baseline characteristics of participants are shown in Table 1. No significant differences were observed between the two groups regarding the age (, 0.81), body composition including fat mass and fat-free mass (, 0.84, and 0.42, respectively), energy intake (, 0.70), fasting blood glucose (, 0.08), and lipid profiles such as TG and TC (, 0.77, and 0.62, respectively). Regarding the status of sex hormones, no significant difference in the testosterone level (, 0.12) and the LH/FSH ratio (, 0.31) was observed between the two groups at baseline. The results obtained from the preliminary analysis of atherogenic indices are presented in Table 2. Despite a significant reduction in the atherogenic index of plasma (P_adjusted, <0.001; mean change, −0.02), Castelli risk index I (P_adjusted, 0.002; mean change, −0.12), and II (P_adjusted, 0.003; mean change, −0.07) in the thylakoid group, no significant differences were observed in the AIP, CRI-I, and II indices in the case of controls (P_{crudeoradjusted} > 0.05). TyG-BMI and METS-IR decreased in both the thylakoid and placebo groups ( < 0.001). Following our results in anthropometric indices, a significant reduction in AVI ( for both groups <0.001), BAI ( for both groups <0.001), and ABSI (P_intervention, 0.029 and P_control < 0.001) was found in the thylakoid and placebo groups ( < 0.05). Table 3 shows renal function markers among the two groups of study; no significant differences were found in serum urea, creatinine, and total protein between the baseline and end of the study ( > 0.05). There was a significant increase in creatinine levels in the intervention group (, 0.021), which lost its significance after adjusting for confounding factors (P_adjusted, 0.694). The serum albumin was observed to increase in the thylakoid and placebo groups (mean change for intervention and placebo group, 2.14 and 1.41, respectively; < 0.001), but it disappeared after adjustment for potential confounders both in the intervention and placebo groups ( = 0.955 and 0.768, respectively). Table 4 shows no statistical difference in the mean difference (MD) of AIP (MD, −0.03; 95% CI = −0.06, 0.01; = 0.21), CRI I (MD, −0.22; 95% CI = −0.5, 0.12; = 0.19), CRI II (MD, −0.18; 95% CI = 0.45,0.11; = 0.22), TyG-BMI (MD, −4.32; 95% CI = −17.84, 9.20; = 0.52), METS-IR (MD, −1.28); 95% CI = −3.76, 1.19; = 0.29), BAI (MD, 0.19; 95% CI = −1.13, 1.51; = 0.77), ABSI (MD, <0.001; 95% CI = −0.00, 0.00, 1.51; = 0.12), urea (MD, −2.28; 95% CI = −8.62, 4.06; = 0.47), and albumin (MD, −0.57; 95% CI = −1.18, 0.03; = 0.06 between the thylakoid and placebo groups after 12 weeks of treatment. However, between-group comparison of the effect of 12-week interventions revealed a significant difference in the MD of BMI (MD, −1.64; 95% CI = −0.22, −3.07; = 0.02), AVI (MD, −1.58; 95% CI = −2.58, −0.56; < 0.01), and total protein (MD, −1.78; 95% CI = −2.97, −0.59; < 0.01). There was a high estimated effect size of thylakoid supplementation on the BMI (η² = 0.93), TyG-BMI (η² = 0.13), AVI (η² = 0.54), and total protein (η² = 0.17). Likewise, a low estimated effect size of intervention on the METS-IR (η² = 0.01), urea, and creatinine (η² for both <0.01) is observed in Table 4.

4. Discussion

In the present study, forty-four obese women with PCOS treated with 5 gr thylakoid combined with a hypo-caloric diet showed improved atherogenicity, glycemic, and anthropometric indices, but no significant differences in renal function along the treatment period.

To the best of our knowledge, this trial was the first clinical trial that investigated the effects of thylakoid-rich spinach extract supplementation along with a caloric restriction on novel atherogenic, glycemic, and anthropometric indices in addition to renal function. Supplementation of obese PCOS patients with 5 gr/day thylakoid along with a restricted diet resulted in significant reductions in BMI, AIP, CRI-I, and CRI-II compared to placebo. Meanwhile, other indices including TyG-BMI, METS-IR, AVI, BAI, and ABSI, significantly decreased at the end of the 12-week study in both the thylakoid and placebo groups. Likewise, no meaningful impact was observed on renal function factors including urea, creatinine, albumin, and total protein in any of the intervention and placebo groups.

These results are similar to previous reports where thylakoid supplementation decreased body weight [29, 30, 48–50], glycemic parameters [25, 48, 50], and serum lipid profile [48, 50] which are explained in detail below. A randomized, placebo-controlled study with a twelve-week intervention on 53 healthy nonsmoking females, with a BMI range between 25 and 33 revealed that thylakoids reduced body weight, and total and LDL cholesterol levels [29]. In the previous project with the same population, we reported that supplementation with 5 g/day spinach-derived thylakoid along with a hypo-calorie diet improved traditional anthropometric indices such as BMI and WHR, as well as weight and FM that provides limited information about fat distribution [31]. Considering the need to investigate more appropriate and novel anthropometric indices that combine body shape and disease prediction ability to measure fat distribution, in this study, our investigation showed that thylakoids could also have a beneficial effect on novel indices associated with central obesity and visceral fat distribution. Moreover, in PCOS-induced rats, 8 weeks of thylakoid supplementation at a dose of 6 mg chlorophyll/gr food intake daily by oral gavage for 8 weeks significantly improved the FBS, luteinizing hormone, insulin resistance, and body weight [50]. In addition, thylakoid supplementation along with a high-fat diet for 14 days resulted in increased fecal fat excretion that led to decreased body weight, fat mass, and liver fat accumulation in 30 mice [51]. Köhnke et al. [29] found that a high-fat meal in the combination of thylakoids and pesto resulted in lower levels of ghrelin, serum-free fatty acids, and insulin in normal-weight healthy participants. A double-blind, placebo-controlled, randomized crossover-designed study that was conducted among sixty overweight or obese males and females indicated that supplementation with 5 g of thylakoids could increase satiety as well as a greater increase in the postprandial plasma glucose response compared to the placebo group [25]. Stenblom et al. [52] concluded that the dietary addition of thylakoids to a carbohydrate-rich breakfast resulted in a significant increase in CCK levels postprandially and prevented postprandial hypoglycemia in 20 healthy women.

These observed positive effects of thylakoid extracts on anthropometric indices, glucose homeostasis, and lipid profile could be explained by probable mechanisms, such as lipase/colipase inhibition which stimulates the compensatory release of lipase/colipase and as a mechanism to increase enterostatin which is an appetite suppressant peptide [53]. Thylakoid membranes also delay lipolysis and fat digestion by inhibiting pancreatic lipase/colipase activity that improves the lipid profile [54]. Another possible mechanism is that after consuming a thylakoid-rich meal, cholecystokinin (CCK) secretion increases and postprandial circulating levels of GLP-1 elevate [30], CCK and GLP- 1 can increase insulin secretion, and thylakoids may exert incretin-like effects in this way [53].

The atherogenic index of plasma (AIP) and Castelli indices are used as markers of plasma atherogenicity and are more accurate predictors of cardiovascular risk, especially among individuals with IR [55–57]. In Nawrocka-Rutkowska et al.’s study, the AIP and Castelli index values were higher in the PCOS group with IR compared to the control group [57], and the increased value indicators of atherogenicity indicate that IR has a unique, unfavorable influence on the progression of atherosclerosis. Also, Zhu et al. found a strong association of AIP values with obesity [55]. In the current study, beneficial effect of thylakoid on atherogenicity indices such as AIP, CRI-I, and II can be related to weight loss and central obesity reduction, as well as insulin sensitivity improvement and insulin resistance attenuation following thylakoid supplementation [25, 30, 31, 58]. Furthermore, TyG-BMI, a combination of the TyG index and BMI, has a good performance in the evaluation of IR, and it has also been introduced as a simple and effective index for the evaluation of IR among Chinese women with PCOS [59]. TyG-BMI has also been suggested as a clinical indicator that predicts the occurrence of metabolic syndrome, dysglycemia, and visceral adiposity in women with PCOS [60]. In a two-year prospective cohort study, Bello-Chavolla et al. [61] confirmed that the METS-IR index is a novel score for assessing cardiometabolic risk in healthy and high-risk individuals, as well as a promising tool for screening for insulin sensitivity. Based on the results of the current study, 5 g/day of spinach-derived thylakoid among obese women with PCOS resulted in significant reductions in IR-related indices including TyG-BMI and METS-IR that were observed in the placebo group participants that were under calorie restriction too, so it can be interfered that weight loss is the main core of improvement in TyG-BMI and METS-IR indices. Our results also show that thylakoid membranes supplementation in combination with a hypo-caloric diet significantly affects anthropometric indices including abdominal volume index (AVI), body adiposity index (BAI), and a body shape index (ABSI) that are associated with visceral obesity and body fat distribution [22, 62–64]. Women with PCOS have a similar amount of total and trunk fat as controls but have a larger amount of visceral fat, which is defined by increased thickness of the abdomen fat deposit, particularly in the intraperitoneal area [65]. Visceral adipose tissue (VAT) has fewer insulin receptors located on the cell surface, lower insulin receptor substrate protein-1 expression, and lower insulin receptor affinity. As a result, VAT has less insulin sensitivity and has decreased glucose absorption and utilization [66]. In addition, free fatty acid from VAT lipolysis disrupts the insulin signaling system, reduces liver and skeletal muscle sensitivity to insulin, limits glucose uptake and oxidation, and exacerbates glucose regulation abnormalities [67] (Figure 2).

Figure 2

Hyperandrogenism and insulin resistance are the two main biochemical indicators of polycystic ovary syndrome, which causes disturbances in fat distribution and an increase in abdominal fat and visceral adipose tissue in women with this syndrome. Visceral obesity is associated with impairment of insulin sensitivity, increased free fatty acids as a result of lipolysis, high-triglyceride (TG)/, endothelial dysfunction, and kidney disorders. PCOS, polycystic ovary syndrome; FFA, free fatty acids; VLDL; very low-density lipoprotein.

Considering that obesity, especially visceral obesity, is a risk factor for chronic kidney disease [68, 69], obesity, independent of metabolic problems, contributes to renal dysfunction and structural damage, and so the preventive effect of weight loss on CKD is relatively evident [68]. In overweight or obese diabetic individuals, a lifestyle intervention that included calorie restriction and increased physical activity reduced the incidence of CKD by 30% when compared to controls who received an education intervention [70, 71]. However, the changes observed in renal function factors including urea, creatinine, albumin, and total protein did not differ significantly between the two groups in the present study.

Some of the limitations of the current study should also be addressed; first, our study was conducted among obese subjects with PCOS aged 20–45 years old, and therefore generalization of our results to other populations should be done with caution. Also, since the evaluation of kidney function in this study was done with blood biomarkers, it is better to find the effects of this intervention on kidney function with urinary markers in further studies. Also, due to prescribing a low-calorie diet to participants, it was uncertain whether they would follow the diet. In addition, another limitation of the present study is the relatively small sample size which reflects the need for further studies with a larger sample size to confirm the findings of this study. Although the most accepted and accurate atherogenic, glycemic, and anthropometric indices have been investigated in this study, one of the most challenging and controversial issues is the interpretation of the results, considering that the quality of the surrogate markers has not been definitively established and is controversial. Therefore, the results should be interpreted with caution until further studies confirm the association between each surrogate factor and cardiometabolic risk factors. Our study also has several strengths. To our knowledge, this is the first investigation in a sample of obese PCOS women in which the risk of visceral obesity and renal disorders is assessed based on the novel anthropometric indices and renal function biomarkers. Follow-up of patients in the form of visits once every two weeks and diet according to the condition of each patient, and adjusting the results for potential confounders that increase the reliability of the results are also other strengths of this study.

5. Conclusion

The results of this trial have led us to conclude that 5 gr per day of thylakoid membrane derived from spinach supplementation in 12 weeks modulates atherogenic and anthropometric indices including AIP, CRI-I and II, TyG-BMI, METS-IR, AVI, BAI, and ABSI of obese PCOS women. However, the changes in urea, creatinine, albumin, and total protein were not statistically meaningful.

Data Availability

The data of the current study are available upon a reasonable request to the corresponding author.

Additional Points

Protocol registration number in Iranian Registry of Clinical Trials. IRCT20140907019082N9.

Disclosure

This study was a part of Negin Nikrad’s master’s thesis [72].

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Acknowledgments

The current study was financially supported by Research Undersecretary of Tabriz University of Medical Sciences (Grant number: 69765). The current research was supported by a grant from Research Undersecretary of Tabriz University of Medical Sciences (Identifier: IR.TBZMED.REC.1401.892 and grant number: 69765).

References

Y. Che, J. Yu, Y.-S. Li, Y.-C. Zhu, and T. Tao, “Polycystic ovary syndrome: challenges and possible solutions,” Journal of Clinical Medicine, vol. 12, no. 4, p. 1500, 2023.
View at: Publisher Site | Google Scholar
G. Mirmasoumi, M. Fazilati, F. Foroozanfard et al., “The effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial,” Experimental and Clinical Endocrinology & Diabetes, vol. 126, no. 4, pp. 222–228, 2018.
View at: Publisher Site | Google Scholar
M. Iervolino, E. Lepore, G. Forte, A. S. Laganà, G. Buzzaccarini, and V. Unfer, “Natural molecules in the management of polycystic ovary syndrome (PCOS): an analytical review,” Nutrients, vol. 13, no. 5, p. 1677, 2021.
View at: Publisher Site | Google Scholar
X. Luo, X.-M. Yang, W.-Y. Cai et al., “Decreased sex hormone-binding globulin indicated worse biometric, lipid, liver, and renal function parameters in women with polycystic ovary syndrome,” International journal of endocrinology, vol. 2020, Article ID 7580218, 6 pages, 2020.
View at: Publisher Site | Google Scholar
K. M. Hoeger, A. Dokras, and T. Piltonen, “Update on PCOS: consequences, challenges, and guiding treatment,” Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 3, pp. e1071–e1083, 2021.
View at: Publisher Site | Google Scholar
G. Gallegos-Gonzalez, G. Pineda-García, A. Serrano-Medina, A. L. Martinez, and E. Ochoa-Ruiz, “Association between stress and metabolic syndrome and its mediating factors in university students,” American Journal of Health Behavior, vol. 45, no. 6, pp. 1091–1102, 2021.
View at: Publisher Site | Google Scholar
Y. Du, F. Li, S. Li, L. Ding, and M. Liu, “Causal relationship between polycystic ovary syndrome and chronic kidney disease: a Mendelian randomization study,” Frontiers in Endocrinology, vol. 14, Article ID 1120119, 2023.
View at: Publisher Site | Google Scholar
W. Ye, T. Xie, Y. Song, and L. Zhou, “The role of androgen and its related signals in PCOS,” Journal of Cellular and Molecular Medicine, vol. 25, no. 4, pp. 1825–1837, 2021.
View at: Publisher Site | Google Scholar
P. Anagnostis, B. C. Tarlatzis, and R. P. Kauffman, “Polycystic ovarian syndrome (PCOS): long-term metabolic consequences,” Metabolism, vol. 86, pp. 33–43, 2018.
View at: Publisher Site | Google Scholar
K. Blouin, A. Boivin, and A. Tchernof, “Androgens and body fat distribution,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 108, no. 3-5, pp. 272–280, 2008.
View at: Publisher Site | Google Scholar
G. Ostinelli, S. Laforest, S. G. Denham et al., “Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction,” Journal of Clinical Endocrinology and Metabolism, vol. 107, no. 8, pp. e3330–e3342, 2022.
View at: Publisher Site | Google Scholar
R. Pasquali and C. Oriolo, “Obesity and androgens in women,” Frontiers of Hormone Research, vol. 53, pp. 120–134, 2019.
View at: Publisher Site | Google Scholar
J. Lord and T. Wilkin, “Polycystic ovary syndrome and fat distribution: the central issue?” Human Fertility, vol. 5, no. 2, pp. 67–71, 2002.
View at: Publisher Site | Google Scholar
L. S. Vilmann, E. Thisted, J. L. Baker, and J.-C. Holm, “Development of obesity and polycystic ovary syndrome in adolescents,” Hormone Research in Paediatrícs, vol. 78, no. 5-6, pp. 269–278, 2012.
View at: Publisher Site | Google Scholar
M. Zelenović, T. Kontro, R. C. Dumitru et al., “Leisure-time physical activity and all-cause mortality: a systematic review,” Revista de Psicologia del Deporte, vol. 31, no. 1, 2022.
View at: Google Scholar
G. Şenormancı, Ç. Turan, S. K. Çelik et al., “Gene variants and serum levels of synaptic vesicle and presynaptic plasma membrane proteins in alcohol dependence and their relationship with impulsivity and temperament,” Archives of Clinical Psychiatry (São Paulo), vol. 48, pp. 99–104, 2021.
View at: Google Scholar
S.-H. Zheng and X.-L. Li, “Visceral adiposity index as a predictor of clinical severity and therapeutic outcome of PCOS,” Gynecological Endocrinology, vol. 32, no. 3, pp. 177–183, 2016.
View at: Publisher Site | Google Scholar
Z. C. Guerra, J. R. Moore, T. Londoño, and Y. Castro, “Associations of acculturation and gender with obesity and physical activity among Latinos,” American Journal of Health Behavior, vol. 46, no. 3, pp. 324–336, 2022.
View at: Publisher Site | Google Scholar
L. Wu, W. Zhu, Q. Qiao, L. Huang, Y. Li, and L. Chen, “Novel and traditional anthropometric indices for identifying metabolic syndrome in non-overweight/obese adults,” Nutrition and Metabolism, vol. 18, no. 1, pp. 3–10, 2021.
View at: Publisher Site | Google Scholar
F. Guerrero-Romero and M. Rodrı́guez-Morán, “Abdominal volume index. An anthropometry-based index for estimation of obesity is strongly related to impaired glucose tolerance and type 2 diabetes mellitus,” Archives of Medical Research, vol. 34, no. 5, pp. 428–432, 2003.
View at: Publisher Site | Google Scholar
V. Gowda and K. M. Philip, “Abdominal volume index and conicity index in predicting metabolic abnormalities in young women of different socioeconomic class,” International Journal of Medical Science and Public Health, vol. 5, no. 7, pp. 1452–1456, 2016.
View at: Publisher Site | Google Scholar
B. Jabłonowska-Lietz, M. Wrzosek, M. Włodarczyk, and G. Nowicka, “New indexes of body fat distribution, visceral adiposity index, body adiposity index, waist-to-height ratio, and metabolic disturbances in the obese,” Kardiologia Polska, vol. 75, no. 11, pp. 1185–1191, 2017.
View at: Publisher Site | Google Scholar
H. Bawadi, M. Abouwatfa, S. Alsaeed, A. Kerkadi, and Z. Shi, “Body shape index is a stronger predictor of diabetes,” Nutrients, vol. 11, no. 5, p. 1018, 2019.
View at: Publisher Site | Google Scholar
G. Garab, L. S. Yaguzhinsky, O. Dlouhý, S. V. Nesterov, V. Špunda, and E. S. Gasanoff, “Structural and functional roles of non-bilayer lipid phases of chloroplast thylakoid membranes and mitochondrial inner membranes,” Progress in Lipid Research, vol. 86, Article ID 101163, 2022.
View at: Publisher Site | Google Scholar
C. J. Rebello, J. Chu, R. Beyl, D. Edwall, C. Erlanson-Albertsson, and F. L. Greenway, “Acute effects of a spinach extract rich in thylakoids on satiety: a randomized controlled crossover trial,” Journal of the American College of Nutrition, vol. 34, no. 6, pp. 470–477, 2015.
View at: Publisher Site | Google Scholar
S. Chen, Z. Zhou, and K. Ren, “Influence of sports value on adolescent participation and preference of sci-tech experience activities,” Revista de Psicologia del Deporte, vol. 30, no. 4, 2021.
View at: Google Scholar
E.-L. Stenblom, E. Egecioglu, C. Montelius et al., “Dietary thylakoids reduce visceral fat mass and increase expression of genes involved in intestinal fatty acid oxidation in high-fat fed rats,” American Journal of Physiology- Regulatory, Integrative and Comparative Physiology, vol. 311, no. 3, pp. R618–R627, 2016.
View at: Publisher Site | Google Scholar
S. C. Emek, A. Szilagyi, H.-E. Åkerlund et al., “A large scale method for preparation of plant thylakoids for use in body weight regulation,” Preparative Biochemistry & Biotechnology, vol. 40, no. 1, pp. 13–27, 2009.
View at: Publisher Site | Google Scholar
R. Köhnke, A. Lindqvist, N. Göransson et al., “Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high‐fat fed mice,” Phytotherapy Research, vol. 23, no. 12, pp. 1778–1783, 2009.
View at: Publisher Site | Google Scholar
C. Montelius, D. Erlandsson, E. Vitija, E.-L. Stenblom, E. Egecioglu, and C. Erlanson-Albertsson, “Body weight loss, reduced urge for palatable food and increased release of GLP-1 through daily supplementation with green-plant membranes for three months in overweight women,” Appetite, vol. 81, pp. 295–304, 2014.
View at: Publisher Site | Google Scholar
F. P. F. Tabrizi, M. A. Farhangi, M. Vaezi, and S. Hemmati, “The effects of spinach-derived thylakoid supplementation in combination with calorie restriction on anthropometric parameters and metabolic profiles in obese women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled clinical trial,” Nutrition Journal, vol. 19, no. 1, pp. 82–13, 2020.
View at: Publisher Site | Google Scholar
J. Xavier, C. P. Farias, M. S. P. Soares et al., “Ayahuasca prevents oxidative stress in a rat model of depression elicited by unpredictable chronic mild stress,” Archives of Clinical Psychiatry (São Paulo), vol. 48, pp. 90–98, 2021.
View at: Google Scholar
E. Jovanovski, L. Bosco, K. Khan et al., “Effect of spinach, a high dietary nitrate source, on arterial stiffness and related hemodynamic measures: a randomized, controlled trial in healthy adults,” Clinical Nutrition Research, vol. 4, no. 3, pp. 160–167, 2015.
View at: Publisher Site | Google Scholar
M. F. Saad, M. Rewers, J. Selby et al., “Insulin resistance and hypertension: the insulin resistance atherosclerosis study,” Hypertension, vol. 43, no. 6, pp. 1324–1331, 2004.
View at: Publisher Site | Google Scholar
P. Sivasankaran, K. Hyder, J. Mohan, V. Varma, and D. Raja, “Effects of muscle–specific exercises compared to existing interventions on insulin resistance among prediabetes population of south India,” Journal of Natural Science, Biology and Medicine, vol. 12, no. 2, p. 230, 2021.
View at: Publisher Site | Google Scholar
J. P. Law, L. Pickup, D. Pavlovic, J. N. Townend, and C. J. Ferro, “Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations,” Journal of Human Hypertension, vol. 37, no. 1, pp. 1–19, 2023.
View at: Publisher Site | Google Scholar
Z. Yu, C. M. Rebholz, E. Wong et al., “Association between hypertension and kidney function decline: the Atherosclerosis Risk in Communities (ARIC) study,” American Journal of Kidney Diseases, vol. 74, no. 3, pp. 310–319, 2019.
View at: Publisher Site | Google Scholar
H. F. Chung, A. Al Mamun, M. C. Huang et al., “Obesity, weight change, and chronic kidney disease in patients with type 2 diabetes mellitus: a longitudinal study in Taiwan: 2型糖尿病患者的肥胖、体重改变及慢性肾病的风险:台湾地区的一项纵向研究,” Journal of Diabetes, vol. 9, no. 11, pp. 983–993, 2017.
View at: Publisher Site | Google Scholar
M. Mahdavi-Roshan, M. Mozafarihashjin, N. Shoaibinobarian et al., “Evaluating the use of novel atherogenicity indices and insulin resistance surrogate markers in predicting the risk of coronary artery disease: a case‒control investigation with comparison to traditional biomarkers,” Lipids in Health and Disease, vol. 21, no. 1, p. 126, 2022.
View at: Publisher Site | Google Scholar
R. N. Bergman, D. Stefanovski, T. A. Buchanan et al., “A better index of body adiposity,” Obesity, vol. 19, no. 5, pp. 1083–1089, 2011.
View at: Publisher Site | Google Scholar
A. Afsin, H. Kaya, A. Suner et al., “Plasma atherogenic indices are independent predictors of slow coronary flow,” BMC Cardiovascular Disorders, vol. 21, no. 1, pp. 608-609, 2021.
View at: Publisher Site | Google Scholar
S. Datta Banik, E. Pacheco-Pantoja, R. Lugo et al., “Evaluation of anthropometric indices and lipid parameters to predict metabolic syndrome among adults in Mexico,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, vol. 14, pp. 691–701, 2021.
View at: Publisher Site | Google Scholar
A. Hozhabrnia, S. Jambarsang, and S. M. Namayandeh, “Cut-off values of obesity indices to predict coronary heart disease incidence by time-dependent receiver operating characteristic curve analysis in 10-year follow-up in study of Yazd Healthy Heart Cohort, Iran,” ARYA atherosclerosis, vol. 18, no. 3, pp. 1–10, 2022.
View at: Publisher Site | Google Scholar
Y.-C. Huang, J.-C. Huang, C.-I. Lin et al., “Comparison of innovative and traditional cardiometabolic indices in estimating atherosclerotic cardiovascular disease risk in adults,” Diagnostics, vol. 11, no. 4, p. 603, 2021.
View at: Publisher Site | Google Scholar
J. Yoon, D. Jung, Y. Lee, and B. Park, “The metabolic score for insulin resistance (METS-IR) as a predictor of incident ischemic heart disease: a longitudinal study among Korean without diabetes,” Journal of Personalized Medicine, vol. 11, no. 8, p. 742, 2021.
View at: Publisher Site | Google Scholar
M. Sinaga, M. Worku, T. Yemane et al., “Optimal cut-off for obesity and markers of metabolic syndrome for Ethiopian adults,” Nutrition Journal, vol. 17, no. 1, pp. 109–112, 2018.
View at: Publisher Site | Google Scholar
P. W. Wilson, R. D. Abbott, R. J. Garrison, and W. P. Castelli, “Estimation of very-low-density lipoprotein cholesterol from data on triglyceride concentration in plasma,” Clinical Chemistry, vol. 27, no. 12, pp. 2008–2010, 1981.
View at: Publisher Site | Google Scholar
E. L. S. C. Montelius, C. Montelius, D. Erlandsson et al., “Decreased urge for palatable food after a two-month dietary intervention with green-plant membranes in overweight women,” Journal of Obesity & Weight Loss Therapy, vol. 4, no. 4, 2014.
View at: Publisher Site | Google Scholar
F. Pourteymour Fard Tabrizi, M. Abbasalizad Farhangi, M. Vaezi, and S. Hemmati, “Changes of body composition and circulating neopterin, omentin‐1, and chemerin in response to thylakoid‐rich spinach extract with a hypocaloric diet in obese women with polycystic ovary syndrome: a randomized controlled trial,” Phytotherapy Research, vol. 35, no. 5, pp. 2594–2606, 2021.
View at: Publisher Site | Google Scholar
S. Sherafatmanesh, M. Ekramzadeh, N. Tanideh, M.-T. Golmakani, and F. Koohpeyma, “The effects of thylakoid-rich spinach extract and aqueous extract of caraway (Carum carvi L.) in letrozole-induced polycystic ovarian syndrome rats,” BMC Complementary Medicine and Therapies, vol. 20, no. 1, pp. 249–313, 2020.
View at: Publisher Site | Google Scholar
K. G. Stenkula, E.-L. Stenblom, C. Montelius, E. Egecioglu, and C. Erlanson-Albertsson, “Thylakoids reduce body fat and fat cell size by binding to dietary fat making it less available for absorption in high-fat fed mice,” Nutrition and Metabolism, vol. 14, pp. 4–8, 2017.
View at: Publisher Site | Google Scholar
E.-L. Stenblom, C. Montelius, K. Östbring et al., “Supplementation by thylakoids to a high carbohydrate meal decreases feelings of hunger, elevates CCK levels and prevents postprandial hypoglycaemia in overweight women,” Appetite, vol. 68, pp. 118–123, 2013.
View at: Publisher Site | Google Scholar
A. Amirinejad, J. Heshmati, and F. Shidfar, “Effects of thylakoid intake on appetite and weight loss: a systematic review,” Journal of Diabetes and Metabolic Disorders, vol. 19, no. 1, pp. 565–573, 2020.
View at: Publisher Site | Google Scholar
F. Pourteymour Fard Tabrizi and M. Abbasalizad Farhangi, “A systematic review of the potential effects of thylakoids in the management of obesity and its related issues,” Food Reviews International, vol. 37, no. 5, pp. 469–490, 2021.
View at: Publisher Site | Google Scholar
X. Zhu, L. Yu, H. Zhou et al., “Atherogenic index of plasma is a novel and better biomarker associated with obesity: a population-based cross-sectional study in China,” Lipids in Health and Disease, vol. 17, no. 1, pp. 37–46, 2018.
View at: Publisher Site | Google Scholar
A. A. Kamoru, O. M. Japhet, A. D. Adetunji et al., “Castelli risk index, atherogenic index of plasma, and atherogenic coefficient: emerging risk predictors of cardiovascular disease in HIV-treated patients,” Saudi J Med Pharm Sci, vol. 4929, pp. 1101–1110, 2017.
View at: Google Scholar
J. Nawrocka-Rutkowska, I. Szydłowska, K. Jakubowska et al., “The role of oxidative stress in the risk of cardiovascular disease and identification of risk factors using AIP and Castelli atherogenicity indicators in patients with PCOS,” Biomedicines, vol. 10, no. 7, p. 1700, 2022.
View at: Publisher Site | Google Scholar
A. Gupta, S. Gupta, D. Rajput, R. Mani, P. Durgapal, and B. Goyal, “Expression of human epidermal growth factor receptor 2, survivin, enhancer of zeste homolog-2, COX-2, p53 and p16 molecular markers in gall bladder carcinoma,” International Hepato-Pancreato-Biliary Association, vol. 23, p. 756, 2021.
View at: Publisher Site | Google Scholar
Y. Zheng, G. Yin, F. Chen, L. Lin, and Y. Chen, “Evaluation of triglyceride glucose index and homeostasis model of insulin resistance in patients with polycystic ovary syndrome,” International Journal of Women's Health, vol. 14, pp. 1821–1829, 2022.
View at: Publisher Site | Google Scholar
R. Li, K. Lam, S. Tam et al., “Prediction of incident metabolic syndrome and dysglycaemia by adiposity and insulin resistance indices in Chinese women with polycystic ovary syndrome: a 4-year longitudinal study,” in Proceedings of the 100th Annual Meeting & Expo of the Endocrine Society (ENDO), Endocrine Society, Chicago, IL, USA, March 2018.
View at: Google Scholar
O. Y. Bello-Chavolla, P. Almeda-Valdes, D. Gomez-Velasco et al., “METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes,” European Journal of Endocrinology, vol. 178, no. 5, pp. 533–544, 2018.
View at: Publisher Site | Google Scholar
M. Gažarová, M. Galšneiderová, and L. Mečiarová, “Obesity diagnosis and mortality risk based on a body shape index (ABSI) and other indices and anthropometric parameters in university students,” Roczniki Panstwowego Zakladu Higieny, vol. 70, no. 3, pp. 267–275, 2019.
View at: Publisher Site | Google Scholar
S. Y. Lokpo, W. Amenyega, P. Doe et al., “Abdominal volume index is a better predictor of visceral fat in patients with type 2 diabetes: a cross-sectional study in Ho municipality, Ghana,” Alexandria Journal of Medicine, vol. 58, no. 1, pp. 85–91, 2022.
View at: Publisher Site | Google Scholar
Z. M. J. Al-Obaidi, Abdul-Rasheed Of, M. F. Mahdi, and A. M. Raauf, “Biological evaluation of newly synthesized spebrutinib analogues: potential candidates with enhanced activity and reduced toxicity profiles,” International Journal of Drug Delivery Technology, vol. 9, no. 3, pp. 339–346, 2019.
View at: Google Scholar
E. Carmina, S. Bucchieri, A. Esposito et al., “Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 7, pp. 2500–2505, 2007.
View at: Publisher Site | Google Scholar
C. Wium, H. B. Eggesbø, T. Ueland et al., “Adipose tissue distribution in relation to insulin sensitivity and inflammation in Pakistani and Norwegian subjects with type 2 diabetes,” Scandinavian Journal of Clinical and Laboratory Investigation, vol. 74, no. 8, pp. 700–707, 2014.
View at: Publisher Site | Google Scholar
O. Varlamov, R. Somwar, A. Cornea, P. Kievit, K. L. Grove, and C. T. Roberts Jr, “Single-cell analysis of insulin-regulated fatty acid uptake in adipocytes,” American Journal of Physiology. Endocrinology and Metabolism, vol. 299, no. 3, pp. E486–E496, 2010.
View at: Publisher Site | Google Scholar
K. Zhang, Q. Li, Y. Chen, N. Wang, and Y. Lu, “Visceral adiposity and renal function: an observational study from SPECT-China,” Lipids in Health and Disease, vol. 16, no. 1, pp. 205–207, 2017.
View at: Publisher Site | Google Scholar
A. Mottaghi, P. Mirmiran, H. Delshad, and F. Azizi, “Effect of different obesity phenotypes on incidence of chronic kidney disease in Tehranian adults,” Journal of the American College of Nutrition, vol. 35, no. 7, pp. 587–596, 2016.
View at: Publisher Site | Google Scholar
The Look AHEAD Research Group, “Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes,” New England Journal of Medicine, vol. 369, no. 2, pp. 145–154, 2013.
View at: Publisher Site | Google Scholar
K. Ruckwongpatr, X. C. Fung, C.-Y. Lin, J. D. Latner, and K. S. O'Brien, “Relationships among physical activity, health-related quality of life, and weight stigma in children in Hong Kong,” American Journal of Health Behavior, vol. 45, no. 5, pp. 828–842, 2021.
View at: Publisher Site | Google Scholar
N. Nikrad, The Effect of Oral Supplement of Thylakoid Intake on Serum Levels of Brain Derived Neurotrophic Factor, Lipopolysaccharide and Several Antioxidant Indices in Obese Women with Polycystic Ovary Syndrome under Hypocaloric Diet, Tabriz University of Medical Sciences, Tabriz, Iran, 2023.

Copyright

Copyright © 2023 Negin Nikrad et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

267

Downloads

189

Citations