Sunny NE, Bril F, Cusi K. (2016) Mitochondrial Adaptation in Nonalcoholic Fatty Liver Disease: Novel Mechanisms and Treatment Strategies. Trends Endocrinol Metab. [Epub ahead of print] Review. PMID: 27986466.
Williams CM, McCue MD, Sunny NE, Szejner-Sigal A, Morgan TJ, Allison DB, Hahn DA. (2016) Cold-adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster. Proc. R. Soc. B. 283(1838). PMID: 27605506.
Patterson RE, Kalavalapalli S, Williams CM, Nautiyal M, Mathew JT, Martinez J, Reinhard MK, McDougall DJ, Rocca JR, Yost RA, Cusi K, Garrett TJ, Sunny NE. (2016) Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity. Am J Physiol Endocrinol Metab. 310(7): E484-94. PMID: 26814015.
Bril F, Kadiyala S, Portillo Sanchez P, Sunny NE, Biernacki D, Maximos M, Kalavalapalli S, Lomonaco R, Suman A, Cusi K. (2016) Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes. J Investig Med. 64(1):63-8. PMID: 26755815.
Satapati S, Kucejova B, Duarte JA, Fletcher JA, Reynolds L, Sunny NE, He T, Nair LA, Livingston K, Fu X, Merritt ME, Sherry AD, Malloy CR, Shelton JM, Lambert J, Parks EJ, Corbin I, Magnuson MA, Browning JD, Burgess SC. (2015) Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. J Clin Invest. 125(12):4447-4462. PMID: 26571396, PMCID: PMC4665800.
Sunny NE, Kalavalapalli S, Bril F, Garrett TJ, Nautiyal M, Mathew JT, Williams CM, Cusi K. (2015) Crosstalk between branched chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab. 309(4):E311- E319. PMID: 26058864, PMCID: PMC4537921.
Méndez-Lucas A, Duarte J, Sunny NE, Satapati S, He T, Fu X, Bermúdez J, Burgess SC, Perales JC. (2013) PEPCK-M expression in mouse liver potentiates, not replaces, PEPCK-C mediated gluconeogenesis. J Hepatol. 59 (1) 105-113. PMID: 23466304.
Lomonaco R, Sunny NE, Bril F, Cusi K. (2013) Nonalcoholic fatty liver disease: Current issues and novel treatment approaches. Drugs. 73 (1) 1-14. PMID: 23329465.
Satapati S*, Sunny NE, Kucejova B, Fu X, He T, Mendez-Lucas A, Shelton JM, Perales JC, Browning JD, Burgess SC. (2012) Elevated TCA cycle function in the pathology of diet induced hepatic insulin resistance and fatty liver. J. Lipid Res. 53(6) 1080-1092. PMID: 22493093.
Sunny NE, Parks EJ, Browning JD, Burgess SC. (2011) Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell Metab.14: 804-810. PMID: 22152305; Highlighted by Nature Reviews Endocrinology, Mitochondrial pathways in NAFLD. Highlighted by Science Daily, Fatty livers are in overdrive.
Sunny NE, Bequette BJ. (2011) Glycerol is a major substrate for glucose, glycogen and non essential amino acid synthesis in late term chicken embryos. J. Anim. Sci. 89: 3945-3953. PMID: 21764833.
Potthoff MJ, Boney-Montoya J, Choi M, He T, Sunny NE, Satapati S, Suino-Powell K, Xu HE, Gerard RD, Finck BN, Burgess SC, Mangelsdorf DJ, Kliewer SA. (2011) FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α Pathway. Cell Metab. 13: 729 - 738.
Kucejova B, Sunny NE, Nguyen AD, Hallac R, Fu X, Pena-Llopis S, Mason RP, DeBerardinis RJ, Xie XJ, DeBose-Boyd R, Kodibagkar V D, Burgess SC, Brugarolas J. (2011) Uncoupling hypoxia signaling from oxygen sensing in the liver results in hypoketotic hypoglycemic death. Oncogene. 30: 2147- 2160. PMID: 21217781; PMCID: PMC3135264
Sunny NE, Satapati S, Fu X, He T, Mehdbeigi R, Spring-Robinson CL, Duarte J, Potthoff M, Browning J, Burgess SC. (2010) Progressive adaptation of ketogenesis in mice fed a high fat diet. Am J Physiol Endocrinol Metab. 298 (6) E1226-35. PMID: 20233938; PMCID: PMC2886525
Sunny NE, Bequette BJ. (2010) Gluconeogenesis differs in developing chick embryos derived from small compared with typical size broiler breeder eggs. J. Anim. Sci. 88:912-921. PMID: 19966165
El-Kadi SW, Baldwin VI RL, McLeod KR, Sunny NE, Bequette BJ. (2009) Glutamate is the major anaplerotic substrate in the tricarboxylic acid cycle of isolated rumen epithelial and duodenal mucosal cells from beef cattle. J Nutr. 139:869-875. PMID: 19282370
Sunny NE, Owens SL, Baldwin VI RL, El-Kadi SW, Bequette BJ. (2007) Salvage of blood urea nitrogen in sheep is highly dependent upon plasma urea concentration and the efficiency of capture within the digestive tract. J. Anim. Sci. 85:1006–13. PMID: 17202392
Bequette BJ, Sunny NE, El-Kadi SW, Owens SL. (2006) Application of stable isotopes and mass isotopomer distribution analysis to the study of intermediary metabolism of nutrients. J. Anim. Sci. 84(E. Suppl.):E50–9. PMID: 16582092
El-Kadi SW, Baldwin VI RL, Sunny NE, Owens SL, Bequette BJ. (2006) Intestinal protein supply alters amino acid, but not glucose, metabolism by the sheep gastrointestinal tract. J. Nutr. 136:1261-9. PMID: 16614414
Our lab is interested in identifying the critical pathways involved in metabolic regulation during growth and development, and also during the onset of metabolic diseases including obesity, type II diabetes mellitus and fatty liver disease. Towards profiling of shared metabolic networks is various organ systems, we utilize stable isotope based techniques for metabolic flux analysis, together with targeted metabolomics of plasma and tissue metabolites. These mass spectrometry and/or nuclear magnetic resonance (NMR) based approaches in combination with standard measures in molecular biology provide us a functional index of tissue specific metabolism.
The biochemistry of metabolism is substantially being altered with the epidemics of obesity, fatty liver and type II diabetes mellitus (T2DM). Our research interest is in identifying shared metabolic defects in pathways of glucose, lipid and protein metabolism, contributing to the progression of insulin resistance, T2DM and fatty liver disease. We are particularly interested in how dynamic alteration in mitochondrial fuel metabolism leads to lipid accumulation (simple steatosis) in the liver and its subsequent transition to nonalcoholic steato-hepatitis (NASH). From our previous research, we have identified overactive hepatic mitochondrial metabolism as a central feature of nonalcoholic fatty liver disease (simple steatosis and NASH). Overactive mitochondrial pathways have the potential to further drive pathways of reactive oxygen species production and inflammation thus potentially aiding the progression of simple steatosis to NASH. Further, our research has also identified an exciting mechanism where impairment in branched chain amino acid (leucine, isoleucine, valine) modulated mitochondrial function contributes to the etiology of nonalcoholic fatty liver disease. Our lab’s overarching goal is to identify mechanisms contributing to dysfunctional mitochondrial oxidative flux and are significant modulators of cellular inflammation and oxidative stress. Agents targeting dysfunctional mitochondrial metabolism could provide a novel treatment strategy for metabolic diseases.