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PMID: 18560532 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis.

Environmental health perspectives ·Vol. 116 ·No. 6 ·2008-06-00 ·Pages 761-8

Arsenescu V, Arsenescu RI, King V, Swanson H, Cassis LA

Abstract

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. 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. 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. Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol-3-phosphate dehydrogenase activity, and expression of peroxisome proliferator-activated receptor gamma, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist alpha-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. Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.

Keywords
adipocyte differentiation aryl hydrocarbon receptor ectopic lipid deposition obesity polychlorinated biphenyl
MeSH Terms
3T3-L1 Cells Adipocytes/cytology,drug effects Adipokines/metabolism Animals Atherosclerosis/chemically induced,pathology Body Weight/drug effects,physiology Cell Differentiation/drug effects Cytokines/metabolism Gene Expression/drug effects Glycerolphosphate Dehydrogenase/metabolism Inflammation Mediators/metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Obesity/chemically induced,pathology PPAR gamma/metabolism Polychlorinated Biphenyls/toxicity Receptors, Aryl Hydrocarbon/genetics,physiology Reverse Transcriptase Polymerase Chain Reaction Weight Gain/drug effects,physiology
Chemicals
Adipokines Cytokines Inflammation Mediators PPAR gamma Receptors, Aryl Hydrocarbon Polychlorinated Biphenyls Glycerolphosphate Dehydrogenase 3,4,3',4'-tetrachlorobiphenyl 2,4,5,2',4',5'-hexachlorobiphenyl
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Arsenescu Violeta
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40536, USA.
Arsenescu Razvan I
King Victoria
Swanson Hollie
Cassis Lisa A
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Article Info
Journal
Environmental health perspectives
Abbr.
Environ Health Perspect
ISSN
0091-6765
DOI
10.1289/ehp.10554
Published
2008-06-00
Pages
761-8
Language
English
Region
United States
NLM ID
0330411
PMCID
PMC2430232
Subset
IM
Grants
NIEHS NIH HHS · P42 ES007380 · United States
NIEHS NIH HHS · P42 ES 007380 · United States
External Links
PubMed source DOI: 10.1289/ehp.10554 PMC Full Text View journal details
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