HYBRID EVENT: You can participate in person at Boston, Massachusetts, USA or Virtually from your home or work.
Sujith Rajan, Speaker at Diabetes conferences
NYU Long Island School of Medicine, United States
Title : Microsomal triglyceride transfer protein regulates intracellular lipolysis in adipocytes independent of its lipid transfer activity


Background: The triglyceride (TG) transfer activity of microsomal triglyceride transfer protein (MTP) is essential for lipoprotein assembly in the liver and intestine; however, its function in adipose tissue, which does not assemble lipoproteins, is unknown. Here we have elucidated the function of MTP in adipocytes.

Approach and results: We demonstrated that MTP is present on lipid droplets in human adipocytes. Adipose-specific MTP deficient (A-Mttp−/−) male and female mice fed an obesogenic diet gained less weight than Mttpf/f mice and had less fat mass and smaller adipocytes. A-Mttp−/− mice showed higher energy expenditure than Mttpf/f mice. During a cold challenge, A-Mttp−/− mice maintained higher body temperature by mobilizing more fatty acids. Biochemical studies indicated that MTP deficiency de-repressed adipose triglyceride lipase (ATGL) activity and increased TG lipolysis. Both wild type MTP and mutant MTP deficient in TG transfer activity interacted with and inhibited ATGL activity. Thus, the TG transfer activity of MTP is not required for ATGL inhibition.

Conclusion: Our findings demonstrate that adipose-specific MTP deficiency increases ATGL-mediated TG lipolysis and enhances energy expenditure, thereby resisting diet-induced obesity. We speculate that the regulatory function of MTP involving protein-protein interactions might have evolved before the acquisition of TG transfer activity in vertebrates. Adipose-specific inhibition of MTP-ATGL interactions may ameliorate obesity while avoiding the adverse effects associated with inhibition of the TG transfer activity of MTP.

Audience Take away:

  • Adipose-specific MTP knockout mice gain less weight on the obesogenic diet.
  • Adipose-specific MTP knockout mice adapt better to cold challenges.
  • Adipocyte MTP regulates basal lipolysis by inhibiting ATGL.
  • Lipid transfer activity of MTP is not essential to inhibit ATGL activity.
  • MTP inhibits ATGL activity by direct protein-protein interactions.


Dr. Sujith Rajan, did his MS in biomedical science from the University of Wolverhmapton, United Kingdom. He joined Central Drug Research Institute in India for his PhD and worked on adipocyte biology. He is currently working as an research associate at NYU Long Island School of Medicine in deciphering the role of microsomal triglyceride transfer protein in adipocyte biology. He is been working in adipocyte biology for more than a decade and has published 30 articles in different peer-reviewed journals. His one of the prominent works highlighted deleterious effect of chronic hyperinsulinemia on brown adipocyte function and insulin sensitivity.