Abstract 1560: Obese Serum Directly Impairs Apolipoprotein B and A Production by Human Hepatocytes
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 and a reduction in serum concentrations of anti-atherogenic apoA-containing particles While the causes of the elevated serum apoB-to-apoA ratio in obesity are not entirely known, hormonal signals in serum are believed to play a major role. Previous studies have indicated that the adipose-tissue derived secretory proteins (adipokines) resistin and adiponectin are candidate molecules in causing the elevated apoB-to-apoA ratio in obesity. We therefore assessed the hypotheses that:
serum from obese humans directly increases apoB production by hepatic cells and directly reduces apoA production by hepatic cells; and
inhibition of resistin and adiponectin in human serum will directly alter the hepatic production of apoA and apoB.
ApoB and apoA expression levels were studied in human cultured hepatic HepG2 cells:
upon incubation for 24 hrs with 10% serum from well-characterized male lean and obese individuals of either European Caucasian (E) or South Asian (SA) descent, or
upon incubation of 10% serum, as in (A), with the addition of antibodies against resistin and adiponectin.
Thereafter, the cell lysates and media were immunoprecipitated and Western blots were performed to determine the expression of apoB and apoA proteins in cells and media. Incubation of HepG2 cells with obese serum (either E or SA) resulted in a greater cellular expression and secretion of apoB and a lower expression of apoA versus lean controls. Furthermore, antibodies against resistin and adiponectin resulted in decreased and increased expression and secretion of apoB, respectively. In conclusion, we have shown for the first time that obese human serum has a direct stimulatory effect on hepatic apoB production and a suppressive effect on hepatic apoA production versus lean controls. Moreover, serum adipokines resistin and adiponectin both play quantitatively important roles in mediating these effects.