Dietary capsaicin prevents nonalcoholic fatty liver disease through transient receptor potential vanilloid 1-mediated peroxisome proliferator-activated receptor δ activation

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid deposition and coincides often with cardiometabolic diseases. Several dietary factors attenuate NAFLD. Here, we report beneficial effects of chronic dietary capsaicin intake on NAFLD which is mediated by the transient receptor potential vanilloid 1 (TRPV1) activation. The results showed that TRPV1 activation by capsaicin reduced free fatty acids (FFAs) induced the intracellular lipid droplets in HepG2 cells and prevented fatty liver in vivo. Chronic dietary capsaicin promoted lipolysis by increasing hepatic phosphorylated hormone-sensitive lipase (phospho-HSL), carnitine palmitoyltransferase 1 (CPT1), and peroxisome proliferator-activated receptor δ (PPARδ) in wild-type (WT) mice. This effect was absent in TRPV1−/− mice. Dietary capsaicin did not affect lipogenesis, as indicated by the detection of hepatic fatty acid synthase (FAS), sterol regulatory element-binding protein-1 (SREBP-1), PPARα, and liver X receptor (LXR) in mice. Importantly, TRPV1 causes PPARδ activation which significantly increased the expression of autophagy-related proteins, such as light chain 3 (LC3)II, Beclin1, Atg5, and Atg7 in HepG2 cells. In the in vivo study, TRPV1 activation by dietary capsaicin enhanced hepatic PPARδ and autophagy-related proteins and reduced hepatic enzymes and inflammatory factor in WT but not TRPV1−/− mice. TRPV1 activation by dietary capsaicin prevents NAFLD through PPARδ-dependent autophagy enhancement in mice. Dietary capsaicin may represent a beneficial intervention in populations at high risk for NAFLD.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

WT:

Wild-type

TRPV1:

Transient receptor potential vanilloid 1

TRPV1−/− :

TRPV1 knockout

FFAs:

Free fatty acids

HSL:

Hormone-sensitive lipase

CPT1:

Carnitine palmitoyltransferase 1

ATGL:

Adipose triglyceride lipase

PPAR:

Peroxisome proliferator-activated receptor

FAS:

Fatty acid synthase

SREBP-1:

Sterol regulatory element-binding protein-1

LXR:

Liver X receptor

LC3:

Light chain 3

LDs:

Lipid droplets

DMEM:

Dulbecco's modified Eagle's medium

FBS:

Fetal bovine serum

CAP:

Capsaicin

CAPZ:

Capsazepine

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

TNFα:

Tumor necrosis factor α

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Acknowledgments

We thank Quan Chen (The State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China) for presenting GFP-LC3 plasmid. We thank Tingbin Cao and Lijuan Wang (Chongqing Institute of Hypertension, China) for technical assistance. We thank Bin Tan (Institute of Pediatrics, Chongqing Medical Science University) for immunofluorescence images. We thank Yu Huang (Chinese University of Hong Kong, China) for critical review of the manuscript.

Sources of Funding

The National Basic Research Program of China (2012CB517805 and 2012CB517806 and 2011CB503902) and the National Natural Science Foundation of China (30890042).

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Correspondence to Daoyan Liu or Zhiming Zhu.

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Qiang Li and Li Li contributed equally to this work.

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Li, Q., Li, L., Wang, F. et al. Dietary capsaicin prevents nonalcoholic fatty liver disease through transient receptor potential vanilloid 1-mediated peroxisome proliferator-activated receptor δ activation. Pflugers Arch - Eur J Physiol 465, 1303–1316 (2013). https://doi.org/10.1007/s00424-013-1274-4

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Keywords

  • Autophagy
  • Lipolysis
  • NAFLD
  • PPARδ
  • TRPV1