The observation that thiazolidinediones enhance skeletal muscle insulin sensitivity in obesity and in patients with non-insulin-dependent diabetes mellitus (NIDDM), by activating PPARgamma, and possibly by inducing its expression, suggests that PPARgamma expression in skeletal muscle plays a key role in determining tissue sensitivity to insulin, and that PPARgamma expression may be decreased in insulin resistant subjects.
Finally peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA levels were significantly lower in visceral adipose tissue in subjects with a BMI <30 kg/m2, but not in obese subjects, indicating that relative PPAR-gamma expression is increased in omental fat in obesity.
Peroxisome proliferator-activated receptor gamma (PPAR gamma) as a transcription factor plays an important role in lipid metabolism, glucose homeostasis, insulin sensitivity, obesity, diabetes, foam cell formation and atherogenesis.
Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice.
Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a)feeding control, which determines the sensations of satiety and hunger through processes that depend on an interplay between internal signals (notably leptin) and environmental factors; b) energy efficiency, in particular the activation of thermogenesis mediated by uncoupling proteins (UCPs) that makes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by which cells specialised in fat storage (adipocytes) are formed, which is controlled by an interplay of transcription factors, including members of the C/EBP, PPARgamma and ADD families.
These observations lend genetic evidence consistent with our hypothesis that PPARG serves as a common, low-penetrance susceptibility gene for cancers of several types, especially those epidemiologically associated with obesity and fat intake.
This review highlights the roles that PPARgamma play in the regulation of gene expression associated with normal cell physiology as well as the pathophysiology of multiple diseases including obesity, diabetes and cancer.
Peroxisome proliferator activated receptor-gamma is an important factor in adipocyte differentiation and energy metabolism and is thus a candidate gene for obesity, insulin resistance and dyslipidaemia.