Here we demonstrate that BMI correlates positively with tumor glucose uptake in breast cancer but negatively with tumor glucose uptake in non-small cell lung cancer using publicly available human PET-CT data.
This study, the first cancer paper from the Perry lab, shows that mitochondrial uncoupling with a controlled release mitochondrial protonophore (see Science 2015 paper below) slows colon cancer growth in two obese mouse models.
Metabolic physiology & pathophysiology
Perry RJ, Zhang D, Guerra MT, Brill AL, Goedeke L, Nasiri AR, Rabin-Court A, Wang Y, Peng L, Dufour S, Zhang Y, Zhang XM, Butrico GM, Toussaint K, Nozaki Y, Cline GW, Petersen KF, Nathanson MH, Ehrlich BE, Shulman GI (in press). Glucagon stimulates gluconeogenesis by InsP3R-I mediated hepatic lipolysis. Nature.
This study demonstrates that glucagon promotes both hepatic mitochondrial oxidation and gluconeogenesis through IP3R1-mediated calcium signaling and identifies short-term glucagon treatment as a therapy for NAFLD in rodents.
Perry RJ, Lyu K, Rabin-Court A, Dong J, Li X, Yang Y, Qing H, Wang A, Yang X, Shulman GI (in press). Leptin Mediates Postprandial Increases in Body Temperature Through Hypothalamic-Adrenomedullary-Adipose Tissue Crosstalk. J. Clin. Invest.
We demonstrate that leptin causes meal thermogenesis after a prolonged fast by stimulating beta-adrenergic activity and lipolysis.
This paper demonstrates that hypercorticosteronemia (due to hypoleptinemia in diabetic ketoacidosis and in starvation, and independent of leptin during insulin-induced hypoglycemia) causes hyperphagia in an AgRP-dependent manner.
In this study we found that in a prolonged fast, hypoleptinemia activates the HPA axis, increasing lipolysis and hepatic acetyl-CoA content to maintain gluconeogenesis; however, as the fast progresses, substrate limitation due to reduced glucose-alanine cycling as a result of hypoglycemia limits hepatic gluconeogenic and oxidative capacity.
This manuscript reports a non-invasive method – measurement of beta-hydroxybutyrate turnover – as a surrogate to measure hepatic acetyl-CoA, the primary allosteric activator of pyruvate carboxylase and thus of gluconeogenesis.
This paper reports a controlled-release mitochondrial protonophore capable of reversing NAFLD, NASH, and liver fibrosis in rodents. This finding has recently been translated to nonhuman primates: Goedeke et al. Sci. Transl. Med. 2019.
This paper demonstrates that acetyl-CoA is the main regulator of the impact of insulin to suppress hepatic gluconeogenesis (by suppressing white adipose tissue lipolysis) and the impact of inflammatory cytokines to promote gluconeogenesis in obesity by increasing lipolysis.