Loss of hepatic CEACAM1: A unifying mechanism linking insulin resistance to obesity and non-alcoholic fatty liver disease

Garrett Heinrich, Hilda E. Ghadieh, Simona Ghanem, Harrison T. Muturi, Khadijeh Rezaei, Qusai Y. Al-Share, Thomas A. Bowman, Deqiang Zhang, Robert S. Garofalo, Lei Yin, Sonia M. Najjar

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11 Citations (Scopus)

Abstract

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 of Ceacam1 manifest 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.

Original languageEnglish
Article number8
JournalFrontiers in Endocrinology
Volume8
Issue numberJAN
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

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Keywords

  • Fatty liver oxidation
  • Insulin clearance
  • Insulin resistance
  • Lipogenesis
  • Lipolysis
  • NAFLD
  • Visceral obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Heinrich, G., Ghadieh, H. E., Ghanem, S., Muturi, H. T., Rezaei, K., Al-Share, Q. Y., Bowman, T. A., Zhang, D., Garofalo, R. S., Yin, L., & Najjar, S. M. (2017). Loss of hepatic CEACAM1: A unifying mechanism linking insulin resistance to obesity and non-alcoholic fatty liver disease. Frontiers in Endocrinology, 8(JAN), [8]. https://doi.org/10.3389/fendo.2017.0008