Loss of Hepatic CEACAM1: A Unifying Mechanism Linking Insulin Resistance to Obesity and Non-Alcoholic Fatty Liver Disease.
The pathogenesis of human non-alcoholic fatty liver disease (NAFLD) remains unclear, in particular in the context of its relationship to insulin resistance and visceral obesity. Work on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in mice has resolved some of the related questions. CEACAM1 promotes insulin clearance by enhancing the rate of uptake of the insulin-receptor complex. It also mediates a negative acute effect of insulin on fatty acid synthase activity. This positions CEACAM1 to coordinate the regulation of insulin and lipid metabolism. Fed a regular chow diet, global null mutation ofCeacam1manifest hyperinsulinemia, insulin resistance, obesity, and steatohepatitis. They also develop spontaneous chicken-wire fibrosis, characteristic of non-alcoholic steatohepatitis. Reduction of hepatic CEACAM1 expression plays a significant role in the pathogenesis of diet-induced metabolic abnormalities, as bolstered by the protective effect of hepatic CEACAM1 gain-of-function against the metabolic response to dietary fat. Together, this emphasizes that loss of hepatic CEACAM1 links NAFLD to insulin resistance and obesity.
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Heritage College of Osteopathic Medicine, Diabetes Institute, Ohio University, Athens, OH, USA.
Garrett
G
Heinrich
Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
Hilda E
HE
Ghadieh
Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
Simona S
SS
Ghanem
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University , Athens, OH , USA.
Harrison T
HT
Muturi
Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
Khadijeh
K
Rezaei
Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
Qusai Y
QY
Al-Share
Center for Diabetes and Endocrine Research (CeDER), College of Medicine and Life Sciences, University of Toledo , Toledo, OH , USA.
Thomas A
TA
Bowman
Department of Molecular and Integrative Physiology, University of Michigan Medical School , Ann Arbor, MI , USA.
Deqiang
D
Zhang
Yale Cancer Center, Office of Research Affairs , New Haven, CT , USA.
Robert S
RS
Garofalo
Department of Molecular and Integrative Physiology, University of Michigan Medical School , Ann Arbor, MI , USA.
Lei
L
Yin
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Heritage College of Osteopathic Medicine, Diabetes Institute, Ohio University, Athens, OH, USA.
Sonia M
SM
Najjar
NAFLD; fatty liver oxidation; insulin clearance; insulin resistance; lipogenesis; lipolysis; visceral obesity