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

• Published in: Toxicology in vitro 2016-12, Vol.37, p.9-14
• Main Authors: Ward, Antonio B., Dail, Mary B., Chambers, Janice E.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - metabolism; Animals; Apolipoprotein B; Apolipoproteins B - metabolism; Biochemical markers; Biodegradation; Carrier Proteins - metabolism; Cell Line, Tumor; Contaminants; DDE; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Dichlorodiphenyl Dichloroethylene - toxicity; Dyslipidemia; Dyslipidemias - metabolism; Epidemiology; Exposure; Fatty acids; Health risks; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatoma; Insecticides; Insecticides - toxicity; Intracellular; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Liver; Metabolism; Nitrous oxide; Oleic acid; Organic chemicals; Organic compounds; Organochlorine compounds; Organochlorines; Proteins; Rats; Risk; Risk analysis; Risk factors; Secretion; Triglycerides; Triglycerides - metabolism
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2016.08.011

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. •The effect of DDE on lipid metabolism was investigated using rodent hepatoma cells.•DDE increased the secretion of apolipoprotein B (ApoB), MTP and Sort-1.•DDE may play a role in dyslipidemia by affecting lipid metabolism and secretion.•DDE exposure may play a role in the dyslipidemia frequently observed in T2D.