title: Transient receptor potential vanilloid type-1 channel regulates diet-induced obesity, insulin resistance, and leptin resistance.
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.
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Hu
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Hsun-Fan
authors.initials: HF
authors.lastname: Wang
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Tsitsilianos
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Umber
authors.initials: U
authors.lastname: Shafiq
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea jason.kim@umassmed.edu kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: *Program in Molecular Medicine and Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Massachusetts Medical School, Worcester, Massachusetts, USA; World Class University Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea; Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea; and Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea jason.kim@umassmed.edu kiwon@snu.ac.kr.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D005947:Glucose
keywords: aging; capsaicin; glucose metabolism; hyperinsulinemic-euglycemic clamp