USP2a Protein Deubiquitinates and Stabilizes the Circadian Protein CRY1 in Response to Inflammatory Signals

“…Adenoviruses were produced in 293AD packaging cells (Agilent Technologies) following LipofectAMINE-mediated transfection (Invitrogen) and concentrated by ultracentrifugation in cesium chloride gradient (31). Adenoviral-mediated CEACAM1 overexpression was confirmed by transducing primary mouse hepatocytes prepared from C57BL/6J mice at 1 × 10 7 particles/well of a 6-well plate for 36 h. CEACAM1 level was determined by immunoblotting with anti-rat CEACAM1 antibody (24).…”

Section: Adenovirus Preparation and Cell Transductionmentioning

confidence: 99%

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

Russo

Ghadieh

Ghanem

et al. 2016

Journal of Lipid Research

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Supplementary key words carcinoembryonic antigen-related cell adhesion molecule 1 • insulin resistance • nicotinic acid • lipolysis • insulin clearanceCirculating insulin levels, in part determined by hepatic insulin clearance, regulate insulin action (1-3). Insulin clearance, which occurs mostly in liver and to a lower extent in kidney, but not in skeletal muscle or white adipose tissue (WAT), plays a pivotal role in promoting insulin sensitivity (4). If impaired, it contributes to mounting hyperinsulinemia in obese humans (5, 6), thus constituting a risk factor for metabolic syndrome (7,8).Our studies on the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane glycoprotein that is highly expressed in liver and kidney, but not WAT or skeletal muscle (9), support these findings. Upon its phosphorylation by the insulin receptor, CEACAM1 promotes insulin clearance by upregulating receptor-mediated insulin uptake into clathrin-coated pits and degradation in hepatocytes (10). Moreover, it mediates a downregulatory effect on mouse fatty acid synthase 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.-Russo, L., H. E. Ghadieh, S. S. Ghanem, Q. Y. Al-Share, Z. N. Smiley, C. Gatto-Weis, E. L. Esakov, M. F. McInerney, G. Heinrich, X. Tong, L. Yin, and S. M. Najjar. Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocytehepatocyte axis.

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“…The general protocol for protein extraction from liver tissue and cells was described previously (41 …”

Section: Protein Extraction Immunoprecipitation and Immunoblottingmentioning

confidence: 99%

E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c and promotes SREBP-1c-mediated lipogenesis

Tong

Zhang

et al. 2016

Journal of Lipid Research

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USP2a Protein Deubiquitinates and Stabilizes the Circadian Protein CRY1 in Response to Inflammatory Signals

Cited by 55 publications

References 78 publications

The intricate dance of post-translational modifications in the rhythm of life

The intricate dance of post-translational modifications in the rhythm of life

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

E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c and promotes SREBP-1c-mediated lipogenesis

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