Journal
GENES
Volume 12, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/genes12050645
Keywords
nuclear receptor; NAFLD; metabolic lipase; obesity; diabetes
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Funding
- Austrian Science Foundation [F7310-B21]
- Austrian Science Fund (FWF)
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Nuclear receptors are ligand-dependent transcription factors with a crucial role in controlling metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and inflammation. Their activity is essential in maintaining metabolic flexibility and is influenced by endogenous ligands.
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 gamma (PPAR gamma) and conversely releases fatty acids as ligands for PPAR alpha, 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.
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