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Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation.
Leeson-Payne, Alasdair; Iyinikkel, Jean; Malcolm, Cameron; Lam, Brian Y H; Sommer, Nadine; Dowsett, Georgina K C; Martinez de Morentin, Pablo B; Thompson, Dawn; Mackenzie, Alasdair; Chianese, Raffaella; Kentistou, Katherine; Gardner, Eugene J; Perry, John R B; Grassmann, Felix; Speakman, John R; Rochford, Justin J; Yeo, Giles S H; Murray, Fiona; Heisler, Lora K.
Affiliation
  • Leeson-Payne A; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Iyinikkel J; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
  • Malcolm C; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
  • Lam BYH; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK.
  • Sommer N; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Dowsett GKC; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK.
  • Martinez de Morentin PB; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Thompson D; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
  • Mackenzie A; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
  • Chianese R; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Kentistou K; Medical Research Council Epidemiology Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Gardner EJ; Medical Research Council Epidemiology Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Perry JRB; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK; Medical Research Council Epidemiology Unit, Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Grassmann F; Institute for Clinical Research and Systems Medicine, Health and Medical University, Potsdam, Germany.
  • Speakman JR; School of Biological Sciences, University of Aberdeen, Aberdeen, UK.
  • Rochford JJ; The Rowett Institute, University of Aberdeen, Aberdeen, UK.
  • Yeo GSH; Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK.
  • Murray F; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. Electronic address: fmurray@abdn.ac.uk.
  • Heisler LK; The Rowett Institute, University of Aberdeen, Aberdeen, UK. Electronic address: lora.heisler@abdn.ac.uk.
Cell Metab ; 36(5): 1076-1087.e4, 2024 May 07.
Article in En | MEDLINE | ID: mdl-38653246
ABSTRACT
Approximately 1 in 4 people worldwide have non-alcoholic fatty liver disease (NAFLD); however, there are currently no medications to treat this condition. This study investigated the role of adiposity-associated orphan G protein-coupled receptor 75 (GPR75) in liver lipid accumulation. We profiled Gpr75 expression and report that it is most abundant in the brain. Next, we generated the first single-cell-level analysis of Gpr75 and identified a subpopulation co-expressed with key appetite-regulating hypothalamic neurons. CRISPR-Cas9-deleted Gpr75 mice fed a palatable western diet high in fat adjusted caloric intake to remain in energy balance, thereby preventing NAFLD. Consistent with mouse results, analysis of whole-exome sequencing data from 428,719 individuals (UK Biobank) revealed that variants in GPR75 are associated with a reduced likelihood of hepatic steatosis. Here, we provide a significant advance in understanding of the expression and function of GPR75, demonstrating that it is a promising pharmaceutical target for NAFLD treatment.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, G-Protein-Coupled / Non-alcoholic Fatty Liver Disease / Mice, Inbred C57BL Limits: Animals / Female / Humans / Male Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2024 Type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, G-Protein-Coupled / Non-alcoholic Fatty Liver Disease / Mice, Inbred C57BL Limits: Animals / Female / Humans / Male Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2024 Type: Article Affiliation country: United kingdom