Abstract 20494: ApoB-lipoproteins Reduce the Efficiency of Fatty Acid Trapping in Human Adipose Tissue
Background: Findings from our lab and others demonstrate that increased numbers of apoB-lipoproteins (plasma apoB) is associated with insulin resistance (IR) and type 2 diabetes in women, independent of inflammation and central adiposity. The mechanism for this association is yet unexplored. Low efficiency of fatty acid (FA) trapping in white adipose tissue (WAT) is known to promote ectopic fat storage and IR in peripheral tissue. Thus, our aim was to explore whether ineffective FA trapping in WAT is a mechanism linking apoB-lipoproteins to IR in women.
Hypotheses: 1) In vivo; postmenopausal obese women with hyperapoB have lower efficiency of postprandial FA trapping in subcutaneous WAT than normoapoB controls and 2) Ex vivo/ in vitro: LDL decrease preadipocyte differentiation and in situ lipoprotein lipase activity in subjects’ WAT and 3T3-L1 adipocytes.
Methods/Results: In vivo; the efficiency of FA trapping in WAT was examined indirectly in 10 non-diabetic obese women with hyperapoB (apoB> 1.2 g/L) vs 10 normoapoB controls (apoB< 1.2 g/L) by following the fate of 13C-triolein labelled high-fat meal in circulation and breath. Preliminary results reveals that, compared to normoapoB controls, hyperapoB women have delayed postprandial 13C-triolein clearance rate (plasma 13C-triglyceride and 13C-FA, p < 0.001) with no difference in 13C-triolein oxidation rate (breath 13CO2 ), suggesting lower 13C-triolein storage rate. Ex vivo/in vitro: 7-days differentiation of 3T3-L1 preadipocytes in the presence of LDL (1.4 g/L) decreased preadipocytes differentiation, evident by smaller lipid droplets and decreased adipocytes in situ lipoprotein lipase activity (i.e. decreased hydrolysis and storage of synthetic 3H-triglyceride rich lipoproteins by adipocytes) (-42 +/- 13%). Moreover, acute exposure of mature 3T3-L1 adipocytes to LDL inhibited in situ lipoprotein lipase activity (up to -30%, 6 hours). Similarly in subjects’ WAT biopsies, 4-hrs exposure to LDL (1.2 g/L) increased accumulation of 3H-triglyceride rich lipoproteins (by 75 +/- 32%, p = 0.04) and of 3H-FA (by 121 +/- 24%, p = 0.008) in the medium.
Conclusion: Both clinical and basic evidences suggest that ineffective FA trapping in WAT may be a novel mechanism linking apoB-lipoproteins to IR in human.
- © 2010 by American Heart Association, Inc.