| First Author | Mukai S | Year | 2021 |
| Journal | J Biol Chem | Pages | 100274 |
| PubMed ID | 33428938 | Mgi Jnum | J:302096 |
| Mgi Id | MGI:6507057 | Doi | 10.1016/j.jbc.2021.100274 |
| Citation | Mukai S, et al. (2021) Adipocyte-specific GPRC6A ablation promotes diet-induced obesity by inhibiting lipolysis. J Biol Chem :100274 |
| abstractText | The G protein-coupled receptor GPRC6A regulates various physiological processes in response to its interaction with multiple ligands such as extracellular basic amino acids, divalent cations, testosterone, and the uncarboxylated form of osteocalcin (GluOC). Global ablation of GPRC6A increases the susceptibility of mice to diet-induced obesity and related metabolic disorders. However, given that GPRC6A is expressed in many tissues and responds to a variety of hormonal and nutritional signals, the cellular and molecular mechanisms underlying the development of metabolic disorders in conventional knockout mice have remained unclear. On the basis of our previous observation that long-term oral administration of GluOC markedly reduced adipocyte size and improved glucose tolerance in wild-type mice, we examined whether GPRC6A signaling in adipose tissue might be responsible for prevention of metabolic disorders. We thus generated adipocyte-specific GPRC6A knockout mice, and we found that these animals manifested increased adipose tissue weight, adipocyte hypertrophy, and adipose tissue inflammation when fed a high-fat, high-sucrose diet compared with control mice. These effects were associated with reduced lipolytic activity due to down-regulation of lipolytic enzymes such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase in adipose tissue of the conditional knockout mice. Given that, among GPR6CA ligands tested, GluOC and ornithine increased the expression of ATGL in cultured 3T3-L1 adipocytes in a manner dependent on GPRC6A, our results suggest that the constitutive activation of GPRC6A signaling in adipocytes by GluOC or ornithine plays a key role in adipose lipid handling and the prevention of obesity and related metabolic disorders. |
