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′-terachlorobiphenyl (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 γ, 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 761-768 |
| Number of pages | 8 |
| Journal | Environmental Health Perspectives |
| Volume | 116 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2008 |
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All Science Journal Classification (ASJC) codes
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis
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Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. / Arsenescu, Violeta; Arsenescu, Razvan I.; King, Victoria; Swanson, Hollie; Cassis, Lisa A.
In: Environmental Health Perspectives, Vol. 116, No. 6, 01.06.2008, p. 761-768.Research output: Contribution to journal › Article
TY - JOUR
T1 - Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis
AU - Arsenescu, Violeta
AU - Arsenescu, Razvan I.
AU - King, Victoria
AU - Swanson, Hollie
AU - Cassis, Lisa A.
PY - 2008/6/1
Y1 - 2008/6/1
N2 - 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′-terachlorobiphenyl (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 γ, 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.
AB - 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′-terachlorobiphenyl (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 γ, 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.
UR - http://www.scopus.com/inward/record.url?scp=46749092580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46749092580&partnerID=8YFLogxK
U2 - 10.1289/ehp.10554
DO - 10.1289/ehp.10554
M3 - Article
C2 - 18560532
AN - SCOPUS:46749092580
VL - 116
SP - 761
EP - 768
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
SN - 0091-6765
IS - 6
ER -