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Toxicol In Vitro. 2016 Dec;37:9-14. doi: 10.1016/j.tiv.2016.08.011. Epub 2016 Aug 23.

In Vitro effect of DDE exposure on the regulation of lipid metabolism and secretion in McA-RH7777 hepatocytes: A potential role in dyslipidemia which may increase the risk of type 2 diabetes mellitus.

Author information

1
Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State MS 39762, United States. Electronic address: abw8022@yahoo.com.
2
Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State MS 39762, United States. Electronic address: med82@msstate.edu.
3
Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State MS 39762, United States. Electronic address: chambers@cvm.msstate.edu.

Abstract

Organochlorine compounds (OC), such as the legacy insecticides, were widespread environmental contaminants. OC including dichlorodiphenyldichloroethylene (DDE), a metabolite of the insecticide DDT, have an epidemiological association with type 2 diabetes mellitus (T2D) and may play a role in risk factors that contribute to T2D such as dyslipidemia. The liver, a potential target for DDE, plays a role in dyslipidemia. The in vitro effect of DDE on hepatocyte lipid metabolism and secretion was investigated using McArdle-RH7777 (McA) rodent hepatoma liver cells. When stimulated by the free fatty acid oleic acid (OA), DDE increased the secretion of apolipoprotein B (ApoB) suggesting a role for DDE in increasing lipid secretion. Intracellular protein levels of microsomal triglyceride transfer protein (MTP) were increased while sortilin-1 (Sort-1) levels were decreased suggesting a role for DDE in increasing lipid transport and decreasing lipid degradation. Neutral lipids such as intracellular triglycerides (TG) were decreased suggesting that DDE may alter lipid accumulation in liver cells. DDE may play a role in dyslipidemia by affecting mechanisms that regulate lipid metabolism and secretion. These in vitro results on biochemical markers of liver cell dyslipidemia support the concept that DDE exposure may play a role in the dyslipidemia frequently observed in T2D.

KEYWORDS:

Diabetes; Lipids; Liver; Organochlorines

PMID:
27565303
DOI:
10.1016/j.tiv.2016.08.011
[Indexed for MEDLINE]

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