The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and modulation of inflammatory genes. The activity of nuclear receptors is key in maintaining metabolic flexibility. Their activity depends on the availability of endogenous ligands, like fatty acids or oxysterols, and their derivatives produced by the catabolic action of metabolic lipases, most of which are under the control of nuclear receptors. For example, adipose triglyceride lipase (ATGL) is activated by peroxisome proliferator-activated receptor γ (PPARγ) and conversely releases fatty acids as ligands for PPARα, therefore, demonstrating the interdependency of nuclear receptors and lipases. The diverse biological functions and importance of nuclear receptors in metabolic syndrome and NAFLD has led to substantial effort to target them therapeutically. This review summarizes recent findings on the roles of lipases and selected nuclear receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.