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Publication
Transient receptor potential vanilloid type-1 channel regulates diet-induced
obesity, insulin resistance, and leptin resistance.
Authors Lee E, Jung DY, Kim JH, Patel PR, Hu X, Lee Y, Azuma Y, Wang HF, Tsitsilianos N,
Shafiq U, Kwon JY, Lee HJ, Lee KW, Kim JK
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Year 2015
Date Published 8/1/2015
Volume : Pages 29 : 3182 - 92
PubMed Reference 25888600
Abstract Insulin resistance is a major characteristic of obesity and type 2 diabetes, but
the underlying mechanism is unclear. Recent studies have shown a metabolic role
of capsaicin that may be mediated via the transient receptor potential vanilloid
type-1 (TRPV1) channel. In this study, TRPV1 knockout (KO) and wild-type (WT)
mice (as controls) were fed a high-fat diet (HFD), and metabolic studies were
performed to measure insulin and leptin action. The TRPV1 KO mice became more
obese than the WT mice after HFD, partly attributed to altered energy balance
and leptin resistance in the KO mice. The hyperinsulinemic-euglycemic clamp
experiment showed that the TRPV1 KO mice were more insulin resistant after HFD
because of the ~40% reduction in glucose metabolism in the white and brown
adipose tissue, compared with that in the WT mice. Leptin treatment failed to
suppress food intake, and leptin-mediated hypothalamic signal transducer and
activator of transcription (STAT)-3 activity was blunted in the TRPV1 KO mice.
We also found that the TRPV1 KO mice were more obese and insulin resistant than
the WT mice at 9 mo of age. Taken together, these results indicate that lacking
TRPV1 exacerbates the obesity and insulin resistance associated with an HFD and
aging, and our findings further suggest that TRPV1 has a major role in
regulating glucose metabolism and hypothalamic leptin's effects in obesity.




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