Insulin acutely decreases hepatic fatty acid synthase activity

Najjar, Sonia M.; Yang, Yan; Fernström, Mats A.; Lee, Sang Jun; DeAngelis, Anthony M.; Rjaily, George A. Abou; Al-Share, Qusai Y.; Dai, Tong; Miller, Tiffany; Ratnam, Shobha; Ruch, Randall J.; Smith, Stuart; Lin, Sue Hwa; Beauchemin, Nicole; Oyarce, Ana María

doi:10.1016/j.cmet.2005.06.001

Cited by 86 publications

(136 citation statements)

References 48 publications

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“…However, when acutely elevated, insulin can reduce liver fat accumulation in normoinsulinaemic mice [29]. Following insulin-induced phosphorylation of the insulin receptor and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), the proteins are internalised and interact with FASN, reducing its catalytic activity.…”

Section: Acute Vs Prolonged Exposure To Insulinmentioning

confidence: 99%

Signalling mechanisms linking hepatic glucose and lipid metabolism

2006

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Fatty liver and hepatic triglyceride accumulation are strongly associated with obesity, insulin resistance and type 2 diabetes, and are subject to nutritional influences. Hepatic regulation of glucose and lipid homeostasis is influenced by a complex system of hormones, hormonally regulated signalling pathways and transcription factors. Recently, considerable progress has been made in elucidating molecular pathways and potential factors that are affected in insulin-resistant states. In this review we discuss some of the key factors that are involved in both the regulation of glucose and lipid metabolism in the liver. Understanding the molecular network that links hepatic lipid accumulation and impaired glucose metabolism may provide targets for dietary or pharmacological interventions.

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Section: Acute Vs Prolonged Exposure To Insulinmentioning

confidence: 99%

Signalling mechanisms linking hepatic glucose and lipid metabolism

2006

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“…(Fasn) activity in response to acute rise in insulin in the first hour of refeeding following an overnight fast (11). This positions CEACAM1 to contribute to the regulation of fatty acid oxidation until glycogen repletion is complete (12).…”

Section: Ex Vivo Palmitate Oxidationmentioning

confidence: 99%

“…Then 1 ml of the homogenate was added to a sealed beaker containing 1 ml of solution A and left at 30°C for 45 min. Solution A: 0.2 mM of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate (0.5 mCi/ml) (American Radiolabeled Chemicals Inc.) and 2 mM ATP in incubation buffer (100 mM sucrose, 10 mM Tris-HCl, 5 mM potassium phosphate, 80 mM KCl, 1 mM MgCl 2 , 2 mM l-carnitine, 0.1 mM malic acid, 0.05 mM CoA, 1mM dithiothreitol, 0.2 mM EDTA, and 0.5% BSA, pH 7.4). Benzothonium hydroxide (Sigma-Aldrich) was added to a basket attached to the sealed beaker and the reaction was terminated with perchloric acid to recover the radioactive acid soluble metabolites (29).…”

Section: Ex Vivo Palmitate Oxidationmentioning

confidence: 99%

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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 latter hydrolyses adipocyte triglycerides to release free fatty acids and glycerol into the circulation. When delivered acutely, insulin inhibits fatty acid synthase while chronic hyperinsulinaemia (as occurs in insulin resistance) may induce fatty acid synthase activity and increase fatty acid synthesis [2]. The net effect of elevated insulin in normal healthy individuals is to reduce circulating glucose and free fatty acid levels.…”

Section: Introductionmentioning

confidence: 99%