TRPC1 regulates brown adipose tissue activity in a PPARγ-dependent manner

Abstract

Brown adipose tissue (BAT) has the unique ability of converting energy stored in the form of triglycerides into heat. This property makes BAT a target tissue to increase energy expenditure and improve systemic metabolic control. TRPC1 is a founding member of the TRP protein family that also includes several temperature-sensitive channels. We show that TRPC1 is highly expressed in all adipocyte depots, including BAT, and that Trpc1-deficient mice are prone to weight gain and manifest reduced metabolic control. We also demonstrate that knockdown of TRPC1 in cultured brown adipocytes leads to a downregulation of several metabolic genes, including UCP1 and PPARγ, as well as upregulation of the BAT-specific thermosensitive channel TRPV2, ultimately resulting in impaired respiratory function. We also show that TRPC1 is a possible target of PPARγ, suggesting that TRPC1 is a downstream component of a mechanism that translates metabolic or environmental stimuli into output in the form of BAT activity. Better understanding of the possible role of TRPC1 and other TRP channels in body temperature regulation and BAT function may help us to develop obesity therapies based on BAT activation.

Involvement of TRP Channels in Adipocyte Thermogenesis: An Update

“…There is no evidence demonstrate TRPC channels have thermosensitive property so far. TRPC1 is highly expressed in adipocyte depots including BAT and that TRPC1-deficient mice are prone to weight gain and manifest reduced metabolic control ( Wolfrum et al, 2018 ). TRPC1 regulates brown adipocyte activity in a PPARγ-dependent manner, suggesting that TRPC1 is a downstream component of a mechanism that translates metabolic or environmental stimuli into output in the form of BAT activity ( Figure 1 ; Wolfrum et al, 2018 ).…”

“…TRPC1 is highly expressed in adipocyte depots including BAT and that TRPC1-deficient mice are prone to weight gain and manifest reduced metabolic control ( Wolfrum et al, 2018 ). TRPC1 regulates brown adipocyte activity in a PPARγ-dependent manner, suggesting that TRPC1 is a downstream component of a mechanism that translates metabolic or environmental stimuli into output in the form of BAT activity ( Figure 1 ; Wolfrum et al, 2018 ). However, an opposite observation has been reported that fat mass and fasting glucose concentrations were lower in TRPC1KO mice that were fed a HFD (45% fat) ( Krout et al, 2017 ).…”

A Transcriptomic Analysis Reveals Novel Patterns of Gene Expression During 3T3-L1 Adipocyte Differentiation

“…Besides, our data indicated that activation of either TRPV1 or TRPV2 suppresses the differentiation of 3T3-L1 adipocytes. TRPC1 regulates brown adipose tissue activity in a PPARγdependent manner (Wolfrum et al, 2018). TRPV4 is decreased in differentiated adipocytes and is involved in the regulation of adipose oxidative metabolism, inflammation, and energy homeostasis (Ye et al, 2012).…”

A transcriptomic analysis reveals novel patterns of gene expression during 3T3-L1 adipocyte differentiation

“…TRPV2 is up-regulated in matured brown adipocyte and involved in brown adipocyte differentiation [21,44]. Moreover, TRPC1 regulates brown adipose tissue activity in a PPARγdependent manner [45]. TRPV4 is decreased in differentiated adipocyte, and involved in the regulation of adipose oxidative metabolism, inflammation, and energy homeostasis [22].…”