Abstract 18: Adipose Specific Microsomal Triglyceride Transfer Protein Deficient Mice Are Resistant To High Fat Diet Induced Obesity
Microsomal triglyceride transfer protein (MTP) transfers neutral lipids and is essential for the assembly of apolipoprotein B (apoB)-containing lipoproteins by the liver and the small intestine. To determine whether MTP plays a role in adipocyte maturation and lipid metabolism, we used 3T3-L1 preadipocytes. MTP expression and activity transiently increased during early stages of differentiation, and declined later. The increases in MTP expression preceded the expression of PPARγ. Overexpression of MTP enhanced lipid droplet formation in 3T3-L1 cells, and its knockdown attenuated cellular lipid accumulation. These studies indicated that MTP positively affects cellular adipocyte differentiation and adipogenesis. Adipose-specific Mttp gene ablated (A-Mttp-/-) mice were lean and had reduced white adipose tissue after feeding a high-fat diet (HFD) compared with wild-type (Mttpfl/fl) mice. The adipose tissue of A-Mttp-/- mice had increased number of smaller size adipocytes and had less macrophage infiltration as compared with Mttpfl/fl mice. Further, these mice were protected from HFD-induced fatty liver. The A-Mttp-/- mice had moderate increase in plasma triglyceride, but normal cholesterol, glucose and insulin levels. Gene expression analysis showed that the adipose tissue of the A-Mttp-/- mice had significantly lower mRNA levels of PPARγ and its downstream gene targets FAS and FABP4 and lipins. These data suggest that MTP might modulate adipogenesis by influencing PPARγ expression, and plays a role in the accretion of lipids to form larger lipid droplets. Thus agents that inactivate adipose MTP may be useful anti-obesity drugs.
Author Disclosures: A. Bakillah: None. M. Hussain: None.
- © 2015 by American Heart Association, Inc.