The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases

Table 1

Adipokines involved in energy balance/metabolism.

Name	Cell type expression	Biological effects
Leptin: no glycosylated peptide hormone of 16 kDa encoded by the obese (ob) gene, discovered in 1994 by Zhang et al. [18, 19]	Adipocytes: synthesis induced by food intake, eating-related hormones, energy status, and sex hormones (being inhibited by testosterone and increased by ovarian sex steroids) and several proinflammatory mediators (being increased or inhibited by proinflmmatory cytokines with acute or chronic action)	Satiety signal with direct effects on the hypothalamus; stimulates lipolysis; inhibits lipogenesis; improves insulin sensitivity; increases glucose metabolism; and stimulates fatty acid oxidation. Hence, leptin operates as adipostatin and general inductor of energy reserve, being involved in glucose metabolism, synthesis of glucocorticoids. However, it is also known its involvement in other processes, such as the proliferation of lymphocytes (particularly CD4+) and induction of Th1 response, cytokine production, phagocytosis, and regulation of hypothalamic-pituitary-adrenal-axis, reproduction, angiogenesis, and oxidative stress. Collectively, these functions consent to define leptin as a cytokine-like hormone characterised by pleiotropic propriety [18, 19]
Adiponectin: a protein of 30-kDa with a structural homology with collagen VIII and X and complement factor C1q. Once synthesised, it forms trimers which then oligomirize to constitute polymers composed of 4 to 6 trimers. Trimers, hexamers, and high molecular weight (HMW) 12 to-18 mers of adiponectin are present in circulation [18, 19]	Adipocytes	Increases fatty acid oxidation with reduction in plasma fatty acid levels; decreases plasma glucose levels; increases insulin sensitivity; anti-inflammatory, antioxidant, antiatherogenic and anticancer properties through the inhibition TNF-$\alpha$-mediated of NF-$\kappa$B pathway
Resistin: a member of resistin-like molecule (RELMs) family, called “resistin” for its capacity to induce IR in mice. Resistin is also known as member of molecule ‘‘found in inflammatory zone’’ (FIZZ)—family characterised by four members, characterised by a conserved 11-cysteine pattern at the C terminus. Resistin or FIZZ-3 was initially discovered in mice [18, 19]	Adipocytes and M2 macrophages	Induces severe hepatic insulin resistance-increased rate of glucose production in rat (increased resistin plasma concentrations in diet-induced obese mice, but reduced mRNA levels in WAT of obese rodents; stimulates lipolysis); functions controversial in humans
Adipsin: (also called in human complement factor D46) is a rate-limiting enzyme in the alternative pathway of complement activation [18, 19]	Adipocytes and M2 macrophages	Stimulates triglyceride storage, inhibits lipolysis
Apelin: a bioactive peptide, representing endogenous ligand of orphan G-protein-coupled receptor, APJ, homolog to angiotensin II receptor [18, 19]	Adipocytes and stromal vascular cells (in particular macrophages)	Reduces food intake (?); inhibits glucose-induced insulin secretion; antagonize angiotensin II effects in atherosclerosis inducing NO production and inhibiting angiotensin II cellular signaling (? However, there are contrasting literature data).
Visfatin: An insulin mimetic adipokine recently discovered and released prevalently by visceral WAT. Visfatin is also identical to pre-B-cell colony-enhancing factor (PBEF), a cytokine that has been observed increased both in bronchoalveolar lavage fluid in animal models and in neutrophils in septic conditions Under endotoxin stimulation, PBEF/visfatin is produced by neutrophils, inhibiting neutrophil apoptosis [18, 19]	Adipocytes Under endotoxin stimulation, PBEF/visfatin/NAMPT is also produced by neutrophils, inhibiting neutrophil apoptosis	Insulin-mimetic effects; hypoglycaemic effects by stimulating glucose uptake; promotes insulin sensitivity; proadipogenic and lipogenic action. It also induces chemotaxis and the production of IL-1β, TNF-α, and IL6 in CD14+ monocytes and increases proliferative responses in lymphocytes. In addition, visfatin seems to have a nicotinamide adenine dinucleotide (NAD) biosynthetic activity in pancreatic $\beta$ cells [49]. Hence, visfatin acts as nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme that converts nicotinamide (a form of vitamin B3) to nicotinamide mononucleotide (NMN), and a NAD precursor [51].
Vaspin: a serpin (serine protease inhibitor) [18, 19]	Adipocytes	Improves insulin sensitivity; suppresses the production of resistin, leptin, and TNF-$\alpha$
Omentin: a secretory protein, recently identified as a new adipokine It is codified by two genes (1 and 2) [18, 19]	Stromal vascular cells (in particular macrophages)	Enhances insulin-stimulated glucose transport in subcutaneous as well as omental adipocytes; modulation of insulin action
Lipocalin-2 (LCN2), also known as 24p3 or neutrophil gelatinase-associated lipocalin (NGAL): a recently indentified adipokine of the superfamily of lipocalins. It is a 25kDa secretory glycoprotein, originally identified in mouse kidney cells and human neutrophil granules. In adipose tissue, it is highly expressed in vivo and in vitro, and its secretion is regulated by the activation of inflammation and infection [58].	Adipocytes and macrophages, but also neutrophils, hepatic and kidney cells	Has different actions, such as apoptosis and innate immunity; affects glucose metabolism and insulin sensitivity; seems to have dual effects on inflammation: pro- and anti-inflammatory effects. So, increased levels of LCN2 in obesity and IR may constitute a protective mechanism against inflammation [58]
Retinol binding protein-4 (RBP4): this protein belongs a the superfamily of lipocalins. And it is a specific carrier for retinol in the blood [58].	Adipocytes	Promotes IR and the type 2 diabetes [58]