Peroxisome proliferator-activated receptor γ (PPARγ) belongs to a family of nuclear receptors that could serve as lipid sensors. PPARγ is the target of a group of insulin sensitizers called thiazolidinediones (TZD) which regulate the expression of genes involved in glucose and lipid metabolism, as well as adipokines that regulate metabolic function in other tissues. Non-alcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and is even higher in patients with obesity and insulin resistance. TZD-mediated activation of PPARγ could serve as a good treatment for NAFLD because TZD have shown anti-fibrogenic and anti-inflammatory effects in vitro, and increase insulin sensitivity in peripheral tissues which improves liver pathology. However, mechanistic studies in mouse models suggest that the activation of PPARγ in hepatocytes might reduce or limit the therapeutic potential of TZD against NAFLD. In this review, we briefly describe the short history of PPAR isoforms, the relevance of their expression in different tissues, as well as the pathogenesis and potential therapeutics for NAFLD. We also discuss some evidence derived from mouse models that could be useful for endocrinologists to assess tissue-specific roles of PPARs, complement reverse endocrinology approaches, and understand the direct role that PPARγ has in hepatocytes and non-parenchymal cells.
Keyphrases
- insulin resistance
- type diabetes
- metabolic syndrome
- adipose tissue
- skeletal muscle
- high fat diet
- fatty acid
- polycystic ovary syndrome
- high fat diet induced
- poor prognosis
- mouse model
- gene expression
- binding protein
- risk factors
- induced apoptosis
- oxidative stress
- weight loss
- physical activity
- risk assessment
- signaling pathway
- cell proliferation
- blood glucose
- endoplasmic reticulum stress