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Obesity and diabetes have emerged as major epidemics and are now recognized as modern life style diseases. Several nuclear receptors have been implicated in regulating fat and glucose homeostasis. We are interested in characterizing the tissue specific roles for Farnesoid X Receptor (Fxr) and its principal target Small Heterodimer Partner (Shp) in regulating the energy metabolism. It is known that both Fxr-/- mice as well as Shp-/- mice are glucose intolerant. Consistent with these data, SNPs in Fxr are associated with fasting hyperglycemia and mutations in the Shp gene are associated with obesity. These findings highlight the importance of Fxr-Shp axis in controlling fat and glucose metabolism. We have recently discovered that combined loss of both Fxr and Shp, lead to an unexpected reduction in fat depots, enhanced glucose control, and resistance to diet induced obesity which is in stark contrast with the results from individual Fxr-/- mice as well as Shp-/- mice. Therefore we will investigate the coordinate role for both Fxr and Shp in protecting against obesity and subsequent diabetes. Apart from regulating fat and glucose Fxr and Shp play a crucial role in bile acid homeostasis. Bile acids are now recognized to affect wide range of cellular functions including fat and glucose metabolism, mitochondrial function, and the composition of the gut microbiota. My laboratory is interested in understanding (i) How bile acids confer resistance to diet-induced obesity? (ii) What are roles for Fxr and Shp in controlling fat metabolism? and (iii) How and When do bile acids cross-talk with the gut microbiota.
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Nano Lettersno. 5 (2024): 1642-1649
biorxiv(2024)
Jiabao Liu, Ainaz Malekoltojari,Anjana Asokakumar,Vimanda Chow,Linhao Li, Hao Li,Marina Grimaldi,Nathanlown Dang, Jhenielle Campbell,Holly Barrett,Jianxian Sun,William Navarre,
Nature communicationsno. 1 (2024): 2563-2563
Journal of the Endocrine Societyno. Supplement_1 (2023)
Hepatology communicationsno. 10 (2023)
The Journal of biological chemistryno. 11 (2023): 105322-105322
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