PPARγ in human and mouse physiology

Abstract

SummaryThe peroxisome proliferator activated receptor gamma (PPARγ) is a member in the nuclear receptor superfamily which mediates part of the regulatory effects of dietary fatty acids on gene expression. As PPARγ also coordinates adipocyte differentiation, it is an important component in storing the excess nutritional energy as fat. Our genes have evolved into maximizing energy storage, and PPARγ has a central role in the mismatch between our genes and our affluent western society which results in a broad range of metabolic disturbances, collectively known as the metabolic syndrome. A flurry of human and mouse studies has shed new light on the mechanisms how the commonly used insulin sensitizer drugs and PPARγ activators, thiazolidinediones, act, and which of their physiological effects are dependent of PPARγ. It is now evident that the full activation of PPARγ is less advantageous than targeted modulation of it's activity. Furthermore, new roles for PPARγ signaling have been discovered in inflammation, bone morphogenesis, endothelial function, cancer, longevity, and atherosclerosis, to mention a few. Here we draw together and discuss these recent advances in the research into PPARγ biology.

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia

“…PPARg mRNA levels showed a conspicuous decrease in all depots evaluated (MEAT, RPAT and EAT) beginning on day 4 following the injection of tumour cells (early-stage cachexia). Ablation of PPARg1 and PPARg2 from the mature adipocytes results in a moderate reduction of adipose mass, which is accompanied by hyperlipidaemia, liver steatosis and protection from high-fat diet-induced increase in adiposity (Jones et al 2005, Heikkinen et al 2007. Given that PPARg is an essential transcriptional regulator of adipogenesis and is required for maintenance of mature adipocyte function, including triglyceride synthesis and storage (Yahagi et al 1999), we also evaluated its protein expression.…”

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

“…PPARγ is an essential nuclear factor probably best understood in relationship to its role in controlling the expression of a number of regulatory genes involved in lipid metabolism and insulin sensitization (reviewed in 38 ). More recently, evidence suggests that PPARγ plays an important role in regulating epithelial proliferation, atherogenesis, carcinogenesis, immune cell function, and inflammation 8,[38][39][40][41] .…”

“…More recently, evidence suggests that PPARγ plays an important role in regulating epithelial proliferation, atherogenesis, carcinogenesis, immune cell function, and inflammation 8,[38][39][40][41] . Within the epidermis, much less is known about the function, mechanisms of activation and target genes for PPARs (reviewed in 32,36 ).…”

Peroxisome proliferator-activated receptor- suppresses CYP11B2 expression and aldosterone production

“…PPARg also is expressed in various tissues involved in metabolic functions including skeletal muscle, liver, and pancreas (Heikkinen et al 2007).…”