Gpr75-deficient mice are protected from high-fat diet-induced obesity.

Autor: Hossain S; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Gilani A; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Pascale J; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Villegas E; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Diegisser D; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Agostinucci K; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Kulaprathazhe MM; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Dirice E; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Garcia V; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA., Schwartzman ML; Department of Pharmacology, New York Medical College School of Medicine, Valhalla, New York, USA.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2023 Apr; Vol. 31 (4), pp. 1024-1037. Date of Electronic Publication: 2023 Feb 28.
DOI: 10.1002/oby.23692
Abstrakt: Objective: G-protein coupled receptor 75 (GPR75) has been identified as the high-affinity receptor of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive and proinflammatory lipid, and mice overproducing 20-HETE have been shown to develop insulin resistance when fed a high-fat diet (HFD), which was prevented by a 20-HETE receptor blocker. Simultaneously, a large-scale exome sequencing of 640,000 subjects identified an association between loss-of-function GPR75 variants and protection against obesity.
Methods: Wild-type (WT) and Gpr75-deficient mice were placed on HFD for 14 weeks, and their obesity phenotype was examined.
Results: Male and female Gpr75 null (knockout [KO]) and heterozygous mice gained less weight than WT mice when placed on HFD. KO mice maintained the same level of energy expenditure during HFD feeding, whereas WT mice showed a significant reduction in energy expenditure. Diet-driven adiposity and adipocyte hypertrophy were greatly lessened in Gpr75-deficient mice. HFD-fed KO mice did not develop insulin resistance. Adipose tissue from Gpr75-deficient mice had increased expression of thermogenic genes and decreased levels of inflammatory markers. Moreover, insulin signaling, which was impaired in HFD-fed WT mice, was unchanged in KO mice.
Conclusions: These findings suggest that GPR75 is an important player in the control of metabolism and glucose homeostasis and a likely novel therapeutic target to combat obesity-driven metabolic disorders.
(© 2023 The Obesity Society.)
Databáze: MEDLINE
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