Title | Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body Composition, Liver Lipid Content, and Hepatic Insulin Signaling. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Corbit KC, Camporez JPaulo G, Edmunds LR, Tran JL, Vera NB, Erion DM, Deo RC, Perry RJ, Shulman GI, Jurczak MJ, Weiss EJ |
Journal | Diabetes |
Volume | 67 |
Issue | 2 |
Pagination | 208-221 |
Date Published | 2018 02 |
ISSN | 1939-327X |
Keywords | Adipose Tissue, Adiposity, Animals, Diet, High-Fat, Insulin Resistance, Janus Kinase 2, Lipid Metabolism, Liver, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Non-alcoholic Fatty Liver Disease, Obesity, Organ Specificity, Phosphoproteins, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-akt, Signal Transduction, Threonine |
Abstract | Disruption of hepatocyte growth hormone (GH) signaling through disruption of (JAK2L) leads to fatty liver. Previously, we demonstrated that development of fatty liver depends on adipocyte GH signaling. We sought to determine the individual roles of hepatocyte and adipocyte on whole-body and tissue insulin sensitivity and liver metabolism. On chow, JAK2L mice had hepatic steatosis and severe whole-body and hepatic insulin resistance. However, concomitant deletion of in hepatocytes and adipocytes (JAK2LA) completely normalized insulin sensitivity while reducing liver lipid content. On high-fat diet, JAK2L mice had hepatic steatosis and insulin resistance despite protection from diet-induced obesity. JAK2LA mice had higher liver lipid content and no protection from obesity but retained exquisite hepatic insulin sensitivity. AKT activity was selectively attenuated in JAK2L adipose tissue, whereas hepatic insulin signaling remained intact despite profound hepatic insulin resistance. Therefore, JAK2 in adipose tissue is epistatic to liver with regard to insulin sensitivity and responsiveness, despite fatty liver and obesity. However, hepatocyte autonomous JAK2 signaling regulates liver lipid deposition under conditions of excess dietary fat. This work demonstrates how various tissues integrate JAK2 signals to regulate insulin/glucose and lipid metabolism. |
DOI | 10.2337/db17-0524 |
Alternate Journal | Diabetes |
PubMed ID | 29203511 |
PubMed Central ID | PMC5780061 |
Grant List | U24 DK076169 / DK / NIDDK NIH HHS / United States K01 DK099402 / DK / NIDDK NIH HHS / United States P30 DK063720 / DK / NIDDK NIH HHS / United States UL1 TR001863 / TR / NCATS NIH HHS / United States P30 DK026743 / DK / NIDDK NIH HHS / United States T32 GM007324 / GM / NIGMS NIH HHS / United States U24 DK059635 / DK / NIDDK NIH HHS / United States R01 DK040936 / DK / NIDDK NIH HHS / United States R01 DK091276 / DK / NIDDK NIH HHS / United States P30 DK045735 / DK / NIDDK NIH HHS / United States T32 DK007052 / DK / NIDDK NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:13pm