PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of a family of nuclear hormone receptors that exert their transcriptional control on genes harboring PPAR-responsive regulatory elements (PPRE) in partnership with retinoid X receptors (RXR). The activation of PPARs coordinated by specific coactivators/repressors regulate networks of genes controlling diverse homeostatic processes involving inflammation, adipogenesis, lipid metabolism, glucose homeostasis, and insulin resistance. Defects in PPARs have been linked to lipodystrophy, obesity, and insulin resistance as a result of the impairment of adipose tissue expandability and functionality. PPARs can act as lipid sensors, and when optimally activated, can rewire many of the metabolic pathways typically disrupted in obesity leading to an improvement of metabolic homeostasis. PPARs also contribute to the homeostasis of adipose tissue under challenging physiological circumstances, such as pregnancy and aging. Given their potential pathogenic role and their therapeutic potential, the benefits of PPARs activation should not only be considered relevant in the context of energy balance-associated pathologies and insulin resistance but also as potential relevant targets in the context of diabetic pregnancy and changes in body composition and metabolic stress associated with aging. Here, we review the rationale for the optimization of PPAR activation under these conditions.

Orlistat‐Induced Gut Microbiota Modification in Obese Mice

“…PPARs can function as lipid sensors and regulate differentiation and metabolism of adipocytes. Defects in PPARs have been observed in obesity and insulin resistance, and activation of PPARs, which plays a crucial role in various homeostatic processes involving metabolism of carbohydrates, protein, and lipids, could ameliorate inflammation and fat accumulation in the adipose tissue [36]. Moreover, we also observed increased adipocytokine signaling pathway in the HFD + ORL group.…”

Short-Term Responses to Fatty Acids on Lipid Metabolism and Adipogenesis in Rainbow Trout (Oncorhynchus mykiss)

“…These mild changes in circulating metabolites could be reflecting quick adjustments in adipose tissue and liver energy balance. In adipose tissue, lipid metabolism homeostasis and adipogenesis are partially controlled by PPARs, which can act as lipid sensors contributing to homeostasis in circumstantial physiological conditions, when activated by PUFA or eicosanoids [53,54]. In our study, the administration of EPA and LA induced an increase in the expression of the transcription factors ppara and pparb, suggesting an activation of FA oxidation to provide energy to the adipocyte.…”

High-Energy Diet and Shorter Light Exposure Drives Markers of Adipocyte Dysfunction in Visceral and Subcutaneous Adipose Depots of Psammomys obesus

“…Previous studies have found that visceral adipocytes are less insulin sensitive and less able to fully differentiate into mature adipocytes compared to subcutaneous adipocytes [28], indicating that impaired adipocyte differentiation occurs in a site-specific manner. C/EBPα and PPARγ are integral drivers of adipocyte differentiation [29,30]. Co-expression of C/EBPα and PPARγ has synergistic effects on adipogenic conversion in vitro [31].…”