The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes

J Biol Chem. 2017 Dec 15;292(50):20799-20807. doi: 10.1074/jbc.M117.809954. Epub 2017 Oct 26.


The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+-permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined. Our results show that TRPC1 functions as a major Ca2+ entry channel in adipocytes. We have also shown that fat mass and fasting glucose concentrations were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice fed a HF diet and exercised. Finally, autophagy markers were decreased and apoptosis markers increased in TRPC1 KO mice fed a HF diet and exercised. Overall, these findings suggest that TRPC1 plays an important role in the regulation of adiposity via autophagy and apoptosis and that TRPC1 inhibits the positive effect of exercise on type II diabetes risk under a HF diet-induced obesity environment.

Keywords: SOCE; TRPC1; calcium; diabetes; exercise; obesity; transient receptor potential channels (TRP channels).

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity
  • Animals
  • Apoptosis
  • Autophagy
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Calcium Signaling*
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diet, High-Fat / adverse effects
  • Gene Expression Regulation
  • Insulin Resistance*
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • Male
  • Mice, 129 Strain
  • Mice, Knockout
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / prevention & control*
  • Physical Conditioning, Animal*
  • Subcutaneous Fat, Abdominal / metabolism
  • Subcutaneous Fat, Abdominal / pathology
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*


  • Biomarkers
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1