005 Obese Human Serum Stimulates Apolipoprotein B Overproduction by Human Hepatocytes

Abstract

BackgroundObese individuals are at high risk of developing cardiovascular diseases, due in large part to their characteristic dyslipidemia, which is an elevation in serum concentrations of atherogenic apolipoprotein B (apoB)-containing particles. While the causes of the elevated serum apoB levels in obesity are not entirely known, hormonal signals in serum are believed to play a major role. Adipose-tissue derived adipokines, resistin and adiponectin, are candidate molecules in causing the elevated apoB in obesity.MethodsWe therefore quantified apoB protein levels in human HepG2 hepatocytes: (A) upon incubation for 24 hrs with 10% serum from well-characterized male lean and obese individuals of either European Caucasian (EC) or South Asian (SA) descent; or (B) upon incubation of serum, as in (A), with the addition of either antibodies against human resistin or purified human adiponectin. Thereafter, cell lysates and media were immunoprecipitated and Western blots were performed to determine the expression of cellular and secreted apoB protein.ResultsIncubation of HepG2 cells with obese serum (either EC or SA), with characteristically elevated serum resistin levels and reduced serum adiponectin levels, resulted in significantly greater (by 80-90%) cellular expression and secretion of apoB versus lean controls. Furthermore, the addition of either antibodies against human resistin or purified human adiponectin resulted in ameliorated cellular expression of apoB by up to 50%.ConclusionWe have shown for the first time that obese human serum has a direct stimulatory effect on hepatic apoB production versus lean controls. Moreover, serum adipokines, resistin and adiponectin, play opposing and quantitatively important roles in mediating these effects. BackgroundObese individuals are at high risk of developing cardiovascular diseases, due in large part to their characteristic dyslipidemia, which is an elevation in serum concentrations of atherogenic apolipoprotein B (apoB)-containing particles. While the causes of the elevated serum apoB levels in obesity are not entirely known, hormonal signals in serum are believed to play a major role. Adipose-tissue derived adipokines, resistin and adiponectin, are candidate molecules in causing the elevated apoB in obesity. Obese individuals are at high risk of developing cardiovascular diseases, due in large part to their characteristic dyslipidemia, which is an elevation in serum concentrations of atherogenic apolipoprotein B (apoB)-containing particles. While the causes of the elevated serum apoB levels in obesity are not entirely known, hormonal signals in serum are believed to play a major role. Adipose-tissue derived adipokines, resistin and adiponectin, are candidate molecules in causing the elevated apoB in obesity. MethodsWe therefore quantified apoB protein levels in human HepG2 hepatocytes: (A) upon incubation for 24 hrs with 10% serum from well-characterized male lean and obese individuals of either European Caucasian (EC) or South Asian (SA) descent; or (B) upon incubation of serum, as in (A), with the addition of either antibodies against human resistin or purified human adiponectin. Thereafter, cell lysates and media were immunoprecipitated and Western blots were performed to determine the expression of cellular and secreted apoB protein. We therefore quantified apoB protein levels in human HepG2 hepatocytes: (A) upon incubation for 24 hrs with 10% serum from well-characterized male lean and obese individuals of either European Caucasian (EC) or South Asian (SA) descent; or (B) upon incubation of serum, as in (A), with the addition of either antibodies against human resistin or purified human adiponectin. Thereafter, cell lysates and media were immunoprecipitated and Western blots were performed to determine the expression of cellular and secreted apoB protein. ResultsIncubation of HepG2 cells with obese serum (either EC or SA), with characteristically elevated serum resistin levels and reduced serum adiponectin levels, resulted in significantly greater (by 80-90%) cellular expression and secretion of apoB versus lean controls. Furthermore, the addition of either antibodies against human resistin or purified human adiponectin resulted in ameliorated cellular expression of apoB by up to 50%. Incubation of HepG2 cells with obese serum (either EC or SA), with characteristically elevated serum resistin levels and reduced serum adiponectin levels, resulted in significantly greater (by 80-90%) cellular expression and secretion of apoB versus lean controls. Furthermore, the addition of either antibodies against human resistin or purified human adiponectin resulted in ameliorated cellular expression of apoB by up to 50%. ConclusionWe have shown for the first time that obese human serum has a direct stimulatory effect on hepatic apoB production versus lean controls. Moreover, serum adipokines, resistin and adiponectin, play opposing and quantitatively important roles in mediating these effects. We have shown for the first time that obese human serum has a direct stimulatory effect on hepatic apoB production versus lean controls. Moreover, serum adipokines, resistin and adiponectin, play opposing and quantitatively important roles in mediating these effects.