Alonge, K. M., Meares, G. P., and Hillgartner, F. B. (2017) “Glucagon and insulin cooperatively stimulate fibroblast growth factor 21 gene transcription by increasing the expression of activating transcription factor 4”. J. Biol. Chem., In press.
Cyphert, H. A., Alonge, K. M., Ippagunta, S. M., and Hillgartner, F. B. (2014) "Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism". PLoS One 9, e94996.
Cyphert, H. A., Ge, X., Kohan, A., Salati, L. M., Zhang, Y., and Hillgartner, F. B. (2012) "Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21". J. Biol. Chem. 287, 25123-25138.
Bhatnagar, S., Damron, H. A., and Hillgartner, F. B. (2009) "Fibroblast growth factor 19: A novel factor that inhibits hepatic fatty acid synthesis". J. Biol. Chem. 284, 10023-10033.
Obesity and Metabolic Disease
My research program is focused on elucidating the mechanisms mediating the nutritional and hormonal regulation of genes involved carbohydrate and lipid metabolism. Initial studies by my laboratory characterized the mechanisms controlling the transcription of lipogenic enzymes by thyroid hormone, insulin, glucagon, fatty acids, and liver X receptor agonists. In 2009, my laboratory transitioned to a new line of research investigating the expression and metabolic effects of a new group of endocrine-like fibroblast growth factors (i.e. FGF19 and FGF21) that exhibited antiobesity, antidiabetes, and lipid lowering activities. We showed that FGF19 suppressed hepatic fatty acid synthesis and lipogenic enzyme expression and proposed that this effect contributed to the beneficial effects of FGF19 on metabolic syndrome. In more recent work, we identified new transcriptional pathways (i.e. bile acids, insulin, and insulin plus glucagon) and a new posttranscriptional pathway (i.e. glucagon) that induced the expression and secretion of FGF21 in liver. We are currently investigating the mechanisms mediating the effects of bile acids, glucagon, insulin, and insulin plus glucagon on FGF21 expression and secretion. We are also investigating the role of bile acids, insulin, and glucagon in mediating the physiological regulation of FGF21 production in humans.