Gpr75-deficient mice are protected from high-fat diet-induced obesity.
Obesity (Silver Spring)
; 31(4): 1024-1037, 2023 04.
Article
de En
| MEDLINE
| ID: mdl-36854900
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Insulinorésistance
/
Alimentation riche en graisse
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Obesity (Silver Spring)
Sujet du journal:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique