Insulin signalling mechanisms for triacylglycerol storage
Program in Molecular Medicine
Insulin; Adipose Tissue; Triglycerides; Insulin Resistance; Lipogenesis
Biochemistry, Biophysics, and Structural Biology | Endocrine System Diseases | Nutritional and Metabolic Diseases | Physiology
Insulin signalling is uniquely required for storing energy as fat in humans. While de novo synthesis of fatty acids and triacylglycerol occurs mostly in liver, adipose tissue is the primary site for triacylglycerol storage. Insulin signalling mechanisms in adipose tissue that stimulate hydrolysis of circulating triacylglycerol, uptake of the released fatty acids and their conversion to triacylglycerol are poorly understood. New findings include (1) activation of DNA-dependent protein kinase to stimulate upstream stimulatory factor (USF)1/USF2 heterodimers, enhancing the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c); (2) stimulation of fatty acid synthase through AMP kinase modulation; (3) mobilisation of lipid droplet proteins to promote retention of triacylglycerol; and (4) upregulation of a novel carbohydrate response element binding protein beta isoform that potently stimulates transcription of lipogenic enzymes. Additionally, insulin signalling through mammalian target of rapamycin to activate transcription and processing of SREBP1c described in liver may apply to adipose tissue. Paradoxically, insulin resistance in obesity and type 2 diabetes is associated with increased triacylglycerol synthesis in liver, while it is decreased in adipose tissue. This and other mysteries about insulin signalling and insulin resistance in adipose tissue make this topic especially fertile for future research.
DOI of Published Version
Diabetologia. 2013 May;56(5):949-64. doi: 10.1007/s00125-013-2869-1. Link to article on publisher's site
Czech, Michael P.; Tencerova, Michaela; Pedersen, David J.; and Aouadi, Myriam, "Insulin signalling mechanisms for triacylglycerol storage" (2013). University of Massachusetts Medical School Faculty Publications. 48.