Yan Zhen Cheng, Liu Dao Yan, Zhang Li Li, Shen Chen Yi, Ma Qun Li, Cao Ting Bing, Wang Li Juan, Nie Hai, Zidek Walter, Tepel Martin, Zhu Zhi Ming
Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China.
Biochem Biophys Res Commun. 2007 Mar 9;354(2):427-33. doi: 10.1016/j.bbrc.2006.12.213. Epub 2007 Jan 9.
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.
肥胖是一个主要的心血管危险因素。我们测试了耐力运动对脂肪组织中1型大麻素受体（CB1）和过氧化物酶体增殖物激活受体δ（PPAR-δ）依赖性途径的影响。雄性Wistar大鼠被随机分配到标准实验室饲料组，以及高脂饮食组，高脂饮食组又分为无规律耐力运动组和有规律耐力运动组。高脂饮食大鼠进行运动可显著降低内脏脂肪量、血压和脂肪细胞大小（均为p<0.05）。高脂饮食诱导的脂肪细胞肥大伴随着脂肪组织中CB1表达的增加，而运动则显著降低了CB1的表达（均为p<0.05）。CB1受体表达和脂肪细胞分化直接受PPAR-δ调控。高脂饮食诱导的脂肪细胞肥大伴随着PPAR-δ的减少。此外，在3T3-L1前脂肪细胞中通过RNA干扰选择性沉默PPAR-δ可使CB1表达从1.00±0.06（n=3）显著增加至1.91±0.06（n=3；p<0.01），并增加脂肪细胞分化，而腺病毒介导的PPAR-δ过表达则显著降低CB1表达至0.39±0.03（n=3；p<0.01），并减少脂肪细胞分化。在CB1拮抗剂利莫那班存在的情况下，刺激的3T3 L1前脂肪细胞中的脂肪细胞分化显著减少。该研究表明，高脂饮食诱导的脂肪细胞肥大与CB1受体表达增加有关，而CB1受体表达直接受PPAR-δ调控。CB1和PPAR-δ均密切参与针对一个最重要的心血管危险因素的治疗干预。
