Nonalcoholic fatty liver disease comprises a wide spectrum of liver injuries from simple steatosis to steatohepatitis and cirrhosis. Nonalcoholic steatohepatitis (NASH) is defined when liver steatosis is associated with inflammation, hepatocyte damage, and fibrosis. A genetic predisposition and environmental insults (ie, dietary habits, obesity) are putatively responsible for NASH progression. Here, we present the impact of the lipid-sensing nuclear receptors in the pathogenesis and treatment of NASH. In detail, we discuss the pros and cons of the putative transcriptional action of the fatty acid sensors (peroxisome proliferator-activated receptors), the bile acid sensor (farnesoid X receptor), and the oxysterol sensor (liver X receptors) in the pathogenesis and bona fide treatment of NASH.
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http://dx.doi.org/10.1016/j.jcmgh.2021.01.012 | DOI Listing |
Environ Sci Technol
February 2025
Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China.
Metabolism-disrupting chemicals (MDCs) have attracted widespread attention due to their contributions to the prevalence of metabolic diseases worldwide. The farnesoid X receptor (FXR) is a typical lipid-sensing nuclear receptor and plays a crucial role in the development of metabolic diseases. However, few studies have examined the FXR activities of environmental samples and the corresponding MDCs.
View Article and Find Full Text PDFProg Lipid Res
November 2024
Toxalim (Research Centre in Toxicology), INRAE, ENVT, INP-Purpan, UPS, Toulouse University, Toulouse, France; Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland. Electronic address:
Peroxisome proliferator-activated receptors (PPARs) constitute a small family of three nuclear receptors that act as lipid sensors, and thereby regulate the transcription of genes having key roles in hepatic and whole-body energy homeostasis, and in other processes (e.g., inflammation), which have far-reaching health consequences.
View Article and Find Full Text PDFFront Mol Med
January 2024
Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
FEBS Lett
December 2024
Metabolic Programming, TUM School of Life Sciences & ZIEL Institute for Food and Health, Gregor-Mendel-Str. 2, 85354, Freising, Germany.
Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.
View Article and Find Full Text PDFACS Chem Biol
July 2023
Department of Comparative Biomedical Sciences, Center for Environmental Health Sciences, Mississippi State University, College of Veterinary Medicine, Mississippi State, Mississippi 39762, United States.
Triacylglycerols (TAGs) are storage forms of fat, primarily found in cytoplasmic lipid droplets in cells. TAGs are broken down to their component free fatty acids by lipolytic enzymes when fuel reserves are required. However, polyunsaturated fatty acid (PUFA)-containing TAGs are susceptible to nonenzymatic oxidation reactions, leading to the formation of oxylipins that are esterified to the glycerol backbone (termed oxTAGs).
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