| Polychlorinated Biphenyl-77 Induces Adipocyte Differentiation and Proinflammatory Adipokines and Promotes Obesity and Atherosclerosis Violeta Arsenescu,1 Razvan I. Arsenescu,2 Victoria King,1,3 Hollie Swanson,4 and Lisa A. Cassis1 1Graduate Center for Nutritional Sciences, 2Division of Digestive Diseases and Nutrition, 3Cardiovascular Research Center, and 4Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, USA Abstract
Background: Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3´,4,4´-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. Objectives: In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. Methods: PCB-77 or 2,2´,4,4,5,5´-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) . For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR) –/– mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE–/– mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Results: Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol-3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor  , whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR–/– mice. ApoE–/– mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Conclusions: Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis. Key words: adipocyte differentiation, aryl hydrocarbon receptor, ectopic lipid deposition, obesity, polychlorinated biphenyl. Environ Health Perspect 116:761–768 (2008) . doi:10.1289/ehp.10554 available via http://dx.doi.org/ [Online 6 March 2008]
Address correspondence to L. Cassis, Graduate Center for Nutritional Sciences, Room 521B, Wethington Building, University of Kentucky, 900 S. Limestone, Lexington, KY 40536 USA. Telephone: (859) 323-4933. Fax: (859) 257-3646. E-mail: lcassis@uky.edu This work was supported by grant P42 ES 007380 (LC) from the National Institute of Environmental Health Sciences. The authors declare they have no competing financial interests. Received 12 June 2007 ; accepted 6 March 2008.
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