GPRC6a is not required for the effects of a high‐protein diet on body weight in mice

Abstract

ObjectiveThe G-protein coupled receptor family C group 6 member A (GPRC6A) is activated by proteinogenic amino acids and may sense amino acids in the gastrointestinal tract and the brain. The study investigated whether GPRC6A was necessary for the effects of low- and high-protein diets on body weight and food intake in mice.MethodsThe role of GPRC6A in mediating the effects of a low-protein diet on body weight was investigated in GPRC6a knockout (GPRC6a-KO) and wild-type (WT) mice fed a control diet (18% protein) or a low-protein diet (6% protein) for 9 days. The role of GPRC6A in mediating the effects of a high-protein diet on body weight was investigated in GPRC6a-KO and WT mice fed a control diet (18% protein) or a high-protein diet (50% protein) for 5 weeks.ResultsA high-protein diet reduced body weight gain and food intake compared with a control diet in both WT and GPRC6a-KO mice. A low-protein diet decreased body weight gain in GPRC6a-KO mice.ConclusionsGPRC6A was not necessary for the effects of a low- or high-protein diet on body weight and likely does not play a role in protein-induced satiety.

Obesity Impairs Oligopeptide/Amino Acid‐Induced Ghrelin Release and Smooth Muscle Contractions in the Human Proximal Stomach

“…Several oligopeptide/AA‐TASRs were expressed in the human mucosa of the proximal gut, but expression of GPRC6A could not be demonstrated even after testing more than 13 different primers. A study in GPRC6A −/− mice showed no crucial role for GPRC6A in protein‐induced satiety and BW loss . Although the highest expression levels of AA‐TASR, with the exception of TAS1R1, were found in the SI, their expression in the stomach argues against the idea that nutrient sensing is limited to the SI .…”

Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function

“…Because of a lack of potent and selective ligands, these suggested functions have mainly been investigated by phenotyping of knock-out mice where the gene function has been destroyed by deletion of exon 6 (Bräuner-Osborne group (17)), exon 2 (Quarles (18) and Karsenty (14) groups), or the full gene (Murphy (19) and Bräuner-Osborne groups (20)). Under normal physiological conditions, these mouse strains have shown very different phenotypes.…”

Pharmacology and physiological function of the orphan GPRC6A receptor

“…They did not suffer from increased body fat mass, insulin resistance or glucose intolerance in contrast to the exon II model . The full locus GPRC6A KO mouse has been reported to have normal basal glucose levels, normal response to a glucose tolerance test, no differences in insulin sensitivity or body composition, which is in accordance with the phenotype of the exon VI KO model . Additionally, the full locus GPRC6A KO mice displayed no susceptibility differences in developing dysmetabolism compared to WT in response to a high‐dose glucocorticoid treatment .…”

“…The Murphy group demonstrated that GPRC6A was not required for the effects of low‐ or high‐protein diets on energy homoeostasis. The full locus KO mice displayed normal food intake and body‐weight when compared to WTs after 9 and 35 days . It remains unknown why the GPRC6A KO mice are more susceptible to high‐fat diet‐induced obesity, while they display normal responses to high‐protein diets, but as mentioned above stress from single housing in a new environment could be a trigger.…”

“…So far, most studies have focused on the potential function of GPRC6A in regulating glucose metabolism . Despite several studies within the field, it remains uncertain if GPRC6A holds a function in various aspects of metabolism.…”