Xanthakos SA, Jenkins TM, Kleiner DE, Boyce TW, Mourya R, Karns R, Brandt ML, Harmon CM, Helmrath MA, Michalsky MP, Courcoulas AP, Zeller MH, Inge TH; Teen-LABS Consortium. High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery. Gastroenterology. 2015 Sep;149(3):623-34.e8.
There is little known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery, and the factors associated with it.
Timchenko NA. Cell-type specific functions of epidermal growth factor receptor are involved in development of hepatocellular carcinoma. Hepatology. 2015 Jul;62(1):314-6.
The epidermal growth factor/epidermal growth factor receptor (EGF-EGFR) signaling regulates the inflammatory microenvirnoment, and associates with development of hepatocellular carcinoma (HCC). In this editorial, Dr. Timchenko has analyzed recently published observations showing that EGFR has opposite functions in different cell types of the liver. EGFR promotes HCC in Kupffer cells of the liver, while it inhibits HCC in hepatocytes. These observations demonstrated that the therapeutic approaches designed should be for a specific inhibition of EGFR only in macrophages, and should not affect EGFR in parenchymal cells given that the latter scenario might promote tumorigenesis.
Valanejad L, Timchenko N. Akt-FoxO1 axis controls liver regeneration. Hepatology. 2016 May;63(5):1424-6.
Liver regeneration after surgical resections is a complex process which includes multiple alterations in gene expression. Despite significant progress in the studies of liver regeneration, there is little known about triggering events. In this article, Valanejad and Timchenko have analyzed findings by Pauta and colleagues that revealed a critical role of serine-threonine kinase Akt/PKB-Foxo1 pathway in liver regeneration. This axis controls at least four highly significant signaling activation of this axis required for liver regeneration.
Shah AS, D’Alessio D, Ford-Adams ME, Desai AP, Inge TH. Bariatric Surgery: A Potential Treatment for Type 2 Diabetes in Youth. Diabetes Care. 2016 Jun; 39(6): 934-40.
In this study, we review the burden of type 2 diabetes in youth including its associated complications. We discuss the outcomes and complications of bariatric surgery in adolescents with diabetes. The conclusion includes recommendations for future research and options for refinement of the use of bariatric surgery in this patient population.
McGrath PS, Watson CL, Ingram C, Helmrath MA, Wells JM. The Basic Helix-Loop-Helix Transcription Factor NEUROG3 Is Required for Development of the Human Endocrine Pancreas. Diabetes. 2015 Jul;64(7):2497-505.
Neurogenin3 (NEUROG3) is a basic helix-loop-helix transcription factor required for development of the endocrine pancreas in mice. In contrast, humans with NEUROG3 mutations are born with endocrine pancreas function, calling into question the requirement of NEUROG3 for human endocrine pancreas development. To test this directly, we generated human embryonic stem cell (hESC) lines and disrupted both alleles of NEUROG3 using CRISPR/Cas9-mediated gene targeting. NEUROG3(-/-) hESC lines efficiently formed pancreatic progenitors but lacked detectible NEUROG3 protein and did not form endocrine cells in vitro. Moreover, NEUROG3(-/-) hESC lines were unable to form mature pancreatic endocrine cells after engraftment of PDX1(+)/NKX6.1(+) pancreatic progenitors into mice. In contrast, a 75-90% knockdown of NEUROG3 caused a reduction, but not a loss, of pancreatic endocrine cell development. We conclude that NEUROG3 is essential for endocrine pancreas development in humans and that as little as 10% NEUROG3 is sufficient for formation of pancreatic endocrine cells.