Obesity, Metabolic Syndrome, and Adipocytes

Table 1

Obesity, metabolic syndrome, adipogenesis, and angiogenesis.

Documented physiology	Reference
Moderate obesity is associated with adipocyte hypertrophy, whereas more severe obesity also involves adipocyte hypertrophy and hyperplasia. In obese pigs, hyperplasia is evident as clusters of small adipocytes.	[26]
Adipose tissue capillary endothelium changes markedly at the ultrastructural and structural level with adipocyte hypertrophy and even more so in obesity. Capillary lumen diameters are reduced considerably. These changes could interfere with the vascular remodeling necessary during adipocyte hypertrophy.	[27]
Angiogenic capacity was determined by quantifying capillary branch formation from human subcutaneous and visceral adipose tissue explants. subcutaneous explants had more capillary sprouting than visceral adipose tissue but this increased sprouting decreased with morbid obesity representing dysfunctional angiogenesis.	[28]
Angiogenesis associated with subcutaneous adipose tissue and visceral adipose tissue from the same obese patients was evaluated by laying adipose tissue on chick chorioallantoïc membranes. The angiogenic potency of adipose tissue was not depot or fat cell size dependent.	[29]
Pangenomic microarray analysis showed that inflammatory markers and acute phase reactants were overexpressed in obese compared to lean human subcutaneous adipose tissue. Modulation of the inflammatory pathways represents a new therapeutic target for the treatment of obesity and related complications. Genes associated with adipogenesis, per se, were not differentially expressed.	[30]
The development of methods for hypoxia detection in adipose tissue has indicated a hypoxia response in adipose tissue in obese animals. Adipose tissue hypoxia (ATH) may provide mechanisms for chronic inflammation, macrophage infiltration, and mitochondrial dysfunction among other features in adipose tissue in obesity. Adipose tissue blood flow associated with a failure in compensatory angiogenesis or vasodilatation may precipitate ATH. Translational studies in humans are necessary to provide conclusive evidence in support of the ATH concept.	[31]
The development and maintenance of the adipocyte extracellular matrix (ECM) is critical to maintain the function of the adipocyte. Hypoxia in obesity may destabilize the ECM resulting in a number of adverse conditions. Adipocyte hypertrophy may adversely influence the adipocyte ECM stability.	[32]
A 12 yr study of 11,326 respondents showed that overweight individuals with basal metabolic indices (BMI) ranging between 25 and 29.9 had 17% less relative risk of mortality than those with BMI below 18.5 or over 35.	[33]
Weight reduction by 5 to 10% of original weight reduces insulin resistance, blood glucose, blood lipids, and blood pressure, suggesting that some individuals adapt to the excess weight.	[4, 34]
Decline in plasma adiponectin or the rise in C-reactive protein, regardless of obesity, appears to be a better predictor of metabolic syndrome than obesity alone.	[35, 36]
The abatement of metabolic syndrome has been attempted through the use of the two isomers of congugated linoleic acid. The CLA trans10, cis12 isomer depresses differentiation of adipocytes by decreasing expression of peroxisome proliferator-activated receptor γ (PPARγ). The dietary provision to rats of mixtures of CLA cis9, trans11 and CLA trans10, cis12, produced from industrial hydrogenation of vegetable oil, abated insulin resistance and normalized glucose tolerance. However, provision of only CLA trans10, cis12 induced insulin resistance in humans and mice, even though it was found to reduce adipogenesis. Normalization of glucose tolerance by the thiazolidinediones (TZD) is mediated by activation of lipogenesis through the PPARγ-dependent transactivation of GLUT4 genes, which encourage glucose uptake and increase lipogenesis, rather than the antilipogenic mechanism suggested for CLA trans10, cis12. In addition, the provision of mixed isomers of CLA to rats, where the CLA cis9, trans11 is a recognized lipogenic factor, normalized insulin resistance, suggesting that limitations to lipogenesis may be involved in the manifestation of metabolic syndrome.	[37–42]