title: Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta.
abstract: Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore, selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/-0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-delta significantly reduced CB1 expression to 0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are intimately involved in therapeutic interventions against a most important cardiovascular risk factor.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Zhen Cheng
authors.initials: ZC
authors.lastname: Yan
authors.forename: Dao Yan
authors.initials: DY
authors.lastname: Liu
authors.forename: Li Li
authors.initials: LL
authors.lastname: Zhang
authors.forename: Chen Yi
authors.initials: CY
authors.lastname: Shen
authors.forename: Qun Li
authors.initials: QL
authors.lastname: Ma
authors.forename: Ting Bing
authors.initials: TB
authors.lastname: Cao
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Hai
authors.initials: H
authors.lastname: Nie
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
authors.forename: Zhi Ming
authors.initials: ZM
authors.lastname: Zhu
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000378:metabolism; D047494:PPAR delta / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D047494:PPAR delta; D043884:Receptor, Cannabinoid, CB1