@article{256388f2803a4c639e05b734bdfde2aa,
title = "Regulation of hepatic energy metabolism and gluconeogenesis by BAD",
abstract = "The homeostatic balance of hepatic glucose utilization, storage, and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. We show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by Bcl-2-associated agonist of cell death (BAD), a protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism toward diminished glycolysis, excess fatty acid oxidation, and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggests that BAD's suppression of gluconeogenesis is actuated by phosphorylation of its BCL-2 homology (BH)-3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phosphomimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin-resistant and high-fat diet models of diabetes and insulin resistance.",
author = "Alfredo Gim{\'e}nez-Cassina and Luisa Garcia-Haro and Choi, {Cheol Soo} and Osundiji, {Mayowa A.} and Lane, {Elizabeth A.} and Hu Huang and Yildirim, {Muhammed A.} and Benjamin Szlyk and Fisher, {Jill K.} and Klaudia Polak and Elaura Patton and Jessica Wiwczar and Marina Godes and Lee, {Dae Ho} and Kirsten Robertson and Sheene Kim and Ameya Kulkarni and Alberto Distefano and Varman Samuel and Gary Cline and Kim, {Young Bum} and Shulman, {Gerald I.} and Danial, {Nika N.}",
note = "Funding Information: We thank J. Quijada for technical assistance and animal husbandry; J. Lemasters for advice on OCR studies; and B. Lowell, P. Puigserver, members of the Spiegelman laboratory, L. Agius, and F. Matschinsky for helpful discussions. A.G.-C. and L.G.-H. were supported by postdoctoral fellowships from the Ministerio de Educaci{\'o}n y Ciencia (MEC, Spain). M.A.O. was supported by a postdoctoral fellowship from the Juvenile Diabetes Research Foundation. N.N.D. is a recipient of the Burroughs Wellcome Fund Career Award in Biomedical Sciences. This work was supported by the US National Institutes of Health grants K01CA10659 (N.N.D.), R01DK078081 (N.N.D.), R01 DK-40936 (G.I.S.), U24 DK-059635 (G.I.S.), and R01DK083567 (Y.-B.K.) and the Korea Healthcare technology R&D Project A102060, Ministry for Health, Welfare & Family Affairs, Republic of Korea (C.S.C.). ",
year = "2014",
month = feb,
day = "4",
doi = "10.1016/j.cmet.2013.12.001",
language = "English (US)",
volume = "19",
pages = "272--284",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",
}