GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues

• DOI: 10.1096/fj.201800171r
• Publication Date: 2018-08-27T17:40:31Z
• Authors: Christopher Lipina; Sarah K. Walsh; Sharon E. Mitchell; John R. Speakman; Cherry L. Wainwright; Harinder S. Hundal
• Keywords: STIMULATION; 0301 basic medicine; Cannabinoid receptor; Supplementary Data; ENDOCANNABINOID LEVELS; Skeletal muscle; Biochemistry; ACTIVATION; Mice; Insulin; Phosphorylation; Receptors, Cannabinoid; Adiposity; Mice, Knockout; /dk/atira/pure/subjectarea/asjc/1300/1303; Adipogenesis; R; name=Biochemistry; MUSCLE; 3. Good health; Adipose Tissue; Liver; OBESITY; POTENTIAL ROLE; Biotechnology; /dk/atira/pure/subjectarea/asjc/1300/1305; Signal Transduction; 570; /dk/atira/pure/subjectarea/asjc/1300/1311; /dk/atira/pure/subjectarea/asjc/1300/1312; name=Genetics; 610; 612; R Medicine; liver; adipogenesis; 03 medical and health sciences; SDG 3 - Good Health and Well-being; 3T3-L1 Cells; Cell Line, Tumor; Genetics; Animals; Humans; skeletal muscle; Muscle, Skeletal; Molecular Biology; Endocannabinoid; CARDIOMETABOLIC RISK-FACTORS; IDENTIFICATION; GLUCOSE-UPTAKE; Research; cannabinoid receptor; name=Biotechnology; endocannabinoid; name=Molecular Biology; Rats; CANNABINOID RECEPTOR GPR55; Biotechnology and Biological Sciences Research Council (BBSRC); Energy Metabolism; Proto-Oncogene Proteins c-akt

ABSTRACT Emerging evidence indicates that G‐protein coupled receptor 55 (GPR55), a nonclassic of the endocannabinoid system is activated by L‐α‐lysophosphatidylinositol and various cannabinoid ligands, may regulate endocrine function energy metabolism. We examined how GPR55 deficiency modulation affects insulin signaling in skeletal muscle, adipose tissue, liver alongside expression analysis proteins implicated action show GPR55‐null mice display decreased sensitivity these tissues, as evidenced reduced phosphorylation PKB/Akt its downstream targets, concomitant with increased adiposity physical activity relative to wild‐type counterparts. Impaired tissue coincided substrate‐1 abundance whereas epididymal fat it was associated 3‐phosphoinoistide lipid phosphatase, phosphatase tensin homolog. In contrast, activation enhanced cultured muscle cells, adipocytes, hepatocytes; this response negated antagonists gene silencing L6 myotubes. Sustained antagonism 3T3‐L1 adipocytes lipogenesis promoted triglyceride accumulation. Our findings identify positive regulator adipogenesis potential therapeutic target for countering obesity‐induced metabolic dysfunction resistance.—Lipina, C., Walsh, S. K., Mitchell, E., Speakman, J. R., Wainwright, C. L., Hundal, H. impaired peripheral tissues. FASEB 33, 1299–1312 (2019). www.fasebj.org