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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #344023

Research Project: Biology of Obesity Prevention

Location: Healthy Body Weight Research

Title: The TRPC1 CA2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes

Author
item Krout, Danielle
item Schaar, Anne - University Of North Dakota
item Sun, Yuyang - University Of North Dakota
item Sukumaran, Pramod - University Of North Dakota
item Roemmich, James
item Singh, Brij - University Of North Dakota
item Larson, Kate

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/26/2017
Publication Date: 12/15/2017
Citation: Krout, D.P., Schaar, A., Sun, Y., Sukumaran, P., Roemmich, J.N., Singh, B.B., Larson, K.J. 2017. The TRPC1 CA2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes. Journal of Biological Chemistry. 292(50):20799-20807. https://doi.org/10.1074/jbc.M117.809954.

Interpretive Summary: In this manuscript, we describe how absence of a functional calcium channel in mice facilitates exercise-induced protection against high-fat diet-induced obesity and type II diabetes risk. Known as the transient receptor potential canonical channel-1 (TRPC1), this channel is found in key metabolic tissues, including adipose tissue, but the role of TRPC1 in the development of obesity or obesity-associated disease risk has yet to be identified. Results presented in this study show that mice without this channel that are fed a high-fat diet and exercised have decreased fat mass and fasting glucose concentrations as well as decreased adipocyte numbers in adipose tissue. We also show that loss of TRPC1 decreases autophagy, a survival mechanism, and increases apoptosis, cell death, suggesting that TRPC1 promotes exercise-induced protection against high-fat diet-induced obesity and type II diabetes.

Technical Abstract: 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, making it a likely candidate for the regulation of cellular energy metabolism. However, the exact role of TRPC1 in development of obesity, adipose tissue mass changes, and obesity-associated metabolic disease risk has not yet been determined. Our results show that TRPC1 functions as a major Ca2+ entry channel in adipocytes and that chow-fed TRPC1 knock-out (KO) mice weigh significantly less than chow-fed control WT mice. 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 to 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, the autophagy markers were decreased, along with a corresponding increase in apoptosis markers in TRPC1 KO mice fed a HF diet and exercised. Overall, these findings suggest that TRPC1 plays an important role in the regulation of body weight and adiposity and that loss of TRPC1 promotes exercise-induced protection against high-fat diet-induced obesity and type II diabetes.