Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance.

TitleTransient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee, E, Jung, DYoung, Kim, JHun, Patel, PR, Hu, X, Lee, Y, Azuma, Y, Wang, H-F, Tsitsilianos, N, Shafiq, U, Kwon, JYeon, Lee, HJoo, Lee, KWon, Kim, JK
JournalFASEB J
Volume29
Issue8
Pagination3182-92
Date Published2015 Aug
ISSN1530-6860
KeywordsAdipose Tissue, Brown, Aging, Animals, Cells, Cultured, Diabetes Mellitus, Type 2, Diet, High-Fat, Dietary Fats, Energy Metabolism, Glucose, Insulin, Insulin Resistance, Leptin, Male, Mice, Mice, Inbred C57BL, Obesity, TRPV Cation Channels
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.

DOI10.1096/fj.14-268300
Alternate JournalFASEB J.
PubMed ID25888600
PubMed Central IDPMC4511197
Grant ListR01-DK080756 / DK / NIDDK NIH HHS / United States
U24-DK093000 / DK / NIDDK NIH HHS / United States
R24 DK090963 / DK / NIDDK NIH HHS / United States
R24-DK090963 / DK / NIDDK NIH HHS / United States
U24 DK093000 / DK / NIDDK NIH HHS / United States
R01 DK080756 / DK / NIDDK NIH HHS / United States