Biologically Active Lipids
Our studies use a variety of technological platforms including chemical and genetic screens to explore functionally active fatty acids and other individual lipids and nutrients which have both critical intracellular functions and provide hormonal signals between adipose tissue and other metabolic organs such as the liver and muscle tissues. Through the use of lipidomics, bioinformatics, and novel physiological systems, we have identified an endogenous nutrient, C16:1n7-palmitoleate, as a lipokine, a fatty acid-based molecule with hormonal function. Lipokine is produced by fat, and subsequently sends signals to the liver to modify hepatic lipogenesis as well as to the muscle to stimulate glucose disposal. Our studies further demonstrated that de novo lipogenesis in adipose tissue is a critical component of metabolic flexibility and homeostasis. Currently, we are exploring the mechanisms of action of this lipokine in search of additional active fatty acid species to study their metabolic effects and signaling mechanisms, and exploring the significance of adipose tissue de novo lipogenesis in systemic metabolism. In addition, we hope to generate additional strategies to leverage these discovery efforts to create novel preventive and therapeutic opportunities against numerous chronic diseases including
obesity, diabetes, and atherosclerosis.
Suggested Readings:
Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell. 2008 Sep 19;134(6):933-44. doi: 10.1016/j.cell.2008.07.048.
Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamisligil GS. Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study. Ann Intern Med. 2010 Dec 21;153(12):790-9. doi: 10.7326/0003-4819-153-12-201012210-00005.
Charles KN, Li M, Engin F, Arruda AP, Inouye K, Hotamışlıgil GS. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins. Cell Reports. 2017 Oct; DOI:10.1016/j.celrep.2017.09.051. Abstract
Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Sci Transl Med. 2019 Apr 24;11(489):eaav0120. doi: 10.1126/scitranslmed.aav0120. Yilmaz M, Claiborn KC, Hotamışlıgil GS. De Novo Lipogenesis Products and Endogenous Lipokines. Diabetes. 2016 Jun; DOI: 10.2337/db160251. Abstract | Full Text