Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis

Lucia Russo, Hilda E. Ghadieh, Simona Ghanem, Qusai Y. Al-Share, Zachary N. Smiley, Cara Gatto-Weis, Emily L. Esakov, Marcia F. McInerney, Garrett Heinrich, Xin Tong, Lei Yin, Sonia M. Najjar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance and mediating suppression of fatty acid synthase activity. Feeding C57BL/6J male mice with a high-fat (HF) diet for 3-4 weeks triggered a >60% decrease in hepatic CEACAM1 levels to subsequently impair insulin clearance and cause systemic insulin resistance and hepatic steatosis. This study aimed at investigating whether lipolysis drives reduction in hepatic CEACAM1 and whether this constitutes a key mechanism leading to diet-induced metabolic abnormalities. Blocking lipolysis with a daily intraperitoneal injection of nicotinic acid in the last two days of a 30-day HF feeding regimen demonstrated that white adipose tissue (WAT)-derived fatty acids repressed hepatic CEACAM1-dependent regulation of insulin and lipid metabolism in 3-month-old male C57BL/6J mice. Adenoviralmediated CEACAM1 redelivery countered the adverse metabolic effect of the HF diet on insulin resistance, hepatic steatosis, visceral obesity, and energy expenditure. It also reversed the effect of HF diet on inflammation and fibrosis in WAT and liver. This assigns a causative role for lipolysis-driven decrease in hepatic CEACAM1 level and its regulation of insulin and lipid metabolism in sustaining systemic insulin resistance, hepatic steatosis, and other abnormalities associated with excessive energy supply.

Original languageEnglish
Pages (from-to)2163-2175
Number of pages13
JournalJournal of Lipid Research
Volume57
Issue number12
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

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Keywords

  • Carcinoembryonic antigen-related cell adhesion molecule 1
  • Insulin clearance
  • Insulin resistance
  • Lipolysis
  • Nicotinic acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Russo, L., Ghadieh, H. E., Ghanem, S., Al-Share, Q. Y., Smiley, Z. N., Gatto-Weis, C., Esakov, E. L., McInerney, M. F., Heinrich, G., Tong, X., Yin, L., & Najjar, S. M. (2016). Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis. Journal of Lipid Research, 57(12), 2163-2175. https://doi.org/10.1194/jlr.M072066