| First Author | Wang Z | Year | 2022 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 323 |
| Issue | 1 | Pages | R81-R97 |
| PubMed ID | 35537100 | Mgi Jnum | J:325671 |
| Mgi Id | MGI:7281009 | Doi | 10.1152/ajpregu.00097.2021 |
| Citation | Wang Z, et al. (2022) Transient receptor potential cation channel 6 (TRPC6) deficiency leads to increased body weight and metabolic dysfunction. Am J Physiol Regul Integr Comp Physiol |
| abstractText | TRPC6, a member of the TRPC family, is expressed in the hypothalamus and modulates cell Ca(2+) influx. However, the role of TRPC6 in controlling metabolic and cardiovascular functions under normal conditions has not been previously determined. Thus, the impacts of TRPC6 deletion on energy balance, metabolic and cardiovascular regulation as well as the anorexic responses to leptin and melanocortin 3/4 receptor (MC3/4R) activation were investigated in this study. Extensive cardiometabolic phenotyping was conducted in male and female TRPC6 knock out (KO) and control mice from 6 to 24 weeks of age to assess mechanisms by which TRPC6 influences regulation of energy balance and blood pressure (BP). We found that TRPC6 KO mice are heavier with greater adiposity, hyperphagic, and have reduced energy expenditure, impaired glucose tolerance, hyperinsulinemia, and increased liver fat compared to controls. TRPC6 KO mice also have smaller brains, reduced POMC mRNA levels in the hypothalamus, and impaired anorexic response to leptin but not to MC3/4R activation. BP and heart rate, assessed by telemetry, were similar in TRPC6 KO and control mice, and BP responses to air-jet stress were attenuated in TRPC6 KO mice despite increased body weight and metabolic disorders that normally raise BP and increase BP responses to stress. Our results provide evidence for a novel and important role of TRPC6 in controlling energy balance, adiposity, and glucose homeostasis, which suggests that normal TRPC6 function may be necessary to link weight gain and hyperleptinemia with BP responses to acute stress. |
