Regulation of Insulin Sensitivity by Adipose Tissue

Research in our laboratory is focused on elucidating the mechanisms for insulin resistance and energy dysregulation in obesity and type 2 diabetes. In particular, we are investigating how adipocytes regulate systemic insulin sensitivity and whole body energy expenditure, using comprehensive approaches including molecular biology, animal physiology and metabolomic analyses.

Currently we are focusing on studying the roles of adipose nicotinamide N-methyltransferase (NNMT) in obesity and type 2 diabetes. NNMT methylates nicotinamide(vitamin B3) using s-adenosylmethionine (SAM) as a methyl donor. Nicotinamide is a precursor of NAD+, a key metabolite in energy metabolism. SAM regulates polyamine metabolism and epigenetic histone methylation. Using tissue-specific genetic mouse models as well as advanced cell culture system, we seek to determine the roles of NAD+, polyamines and histone methylation in NNMT-regulated insulin sensitivity and energy expenditure.

References.

1. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005 Jul 21;436(7049):356-62.  PubMed PMID: 16034410.

2. Yang Q, Eskurza I, Kiernan UA, Phillips DA, Blüher M, Graham TE, Kahn BB. Quantitative measurement of full-length and C-terminal proteolyzed RBP4 in serum  of normal and insulin-resistant humans using a novel mass spectrometry immunoassay. Endocrinology. 2012 Mar;153(3):1519-27. doi: 10.1210/en.2011-1750. Epub 2012 Jan 17. PubMed PMID: 22253430; PubMed Central PMCID: PMC3281532.

3. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB. Nicotinamide N-methyltransferase  knockdown protects against diet-induced obesity. Nature. 2014 Apr 10;508(7495):258-62. doi: 10.1038/nature13198. PubMed PMID: 24717514.