The supply and demand for metabolic energy in cells fluctuates. Therefore, organisms have evolved mechanisms to store metabolic energy. The most efficient and by far the most common way cells store energy is in the form of fat, particularly triacylglycerols (TGs). Although energy storage is inherently beneficial, overeating in today’s society has led to a global obesity and type 2 diabetes epidemic due in part, to the efficiency of these storage mechanisms.
In our laboratory, we study how metabolic energy is stored and how this process contributes to obesity and metabolic disease. In cells, TGs and other neutral lipids are synthesized in the ER and packaged into lipid droplets (LDs), compact cytosolic organelles that also store precursors for membrane and hormone synthesis. When energy is in short supply, lipids are mobilized from LDs. Lipid droplets therefore grow and shrink in cells to maintain lipid levels and meet metabolic demands.
Despite being discovered more than a century ago, many basic questions about LDs remain unanswered. How are LD formed? What controls their shrinkage and expansion? Our laboratory studies these fundamental questions using a wide range of cutting-edge interdisciplinary approaches, including biophysical, biochemical, and cell biological methods.
We also investigate the physiological importance of these lipid storage mechanisms in mouse models of obesity and metabolic disease. For instance, we are determining the physiological roles of different TG synthesis pathways in the lipid storage and secretion in mammalian tissues and the consequences that result when the storage capacity of these lipids is exceeded.
Mejhert N, et al. (2020) Partitioning of MLX-Family Transcription Factors to Lipid Droplets Regulates Metabolic Gene Expression. Mol Cell. 77(6):1251-1264.e9.
Gluchowski NL, et al. (2019) Hepatocyte Deletion of Triglyceride-Synthesis Enzyme Acyl CoA: Diacylglycerol Acyltransferase 2 Reduces Steatosis Without Increasing Inflammation or Fibrosis in Mice. Hepatology. doi: 10.1002/hep.30765.
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Chung J, et al. (2019). LDAF1 and Seipin Form a Lipid Droplet Assembly Complex. Dev Cell. 51(5):551-563.e7.
Chitraju, C, et.al. (2019). The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes. Journal of Lipid Research, 60(6), 1112-1120.
Sui X, et.al. (2018) Cryo-electron microscopy structure of the lipid droplet-formation protein seipin. Cell Biol.217(12):4080-4091
Chitraju C, et al. (2017) Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis. Cell Metab. 407-418.e3.
Wang H, et al. (2016) Seipin is required for converting nascent to mature lipid droplets. Elife.5.pii: e16582.
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