title: 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.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peijian
authors.initials: P
authors.lastname: Wang
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control; D056945:Hep G2 Cells; D006801:Humans; D008066:Lipolysis / Q000187:drug effects; D000071518:Liver X Receptors; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; D005227:Fatty Acids; D000071518:Liver X Receptors; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D057093:Orphan Nuclear Receptors; D047494:PPAR delta; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D002787:Sterol Esterase; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D002211:Capsaicin