scholarly journals Effects of free fatty acid elevation on hepatic insulin resistance and hepatic oxidative stress

2009 ◽  
Vol 17 (23) ◽  
pp. 2405
Author(s):  
Yan Lu ◽  
Ping Han ◽  
Sheng Zhao ◽  
Yong-Yan Zhang ◽  
Bing He ◽  
...  
2009 ◽  
Vol 2 ◽  
pp. BCI.S2996
Author(s):  
Samit Shah ◽  
Arthur G. Cox

Several studies have been conducted to elucidate the role of free fatty acids (FFAs) in the pathogenesis of type 2 diabetes, but the exact molecular mechanism by which FFAs alter glucose metabolism in the liver is still not completely understood. 1 – 4 In a recent publication, Ragheb and coworkers have examined the effect of free fatty acid (FFA) treatment on insulin signaling and insulin resistance by using immunoprecipitation and immunoblotting to study the effect of high concentrations of insulin and FFAs on insulin receptor-beta (IR-β) and downstream elements in the PI3K pathway using the fructose-fed hamster model. 5 Their results clearly show that free fatty acids have an insignificant effect on IR-β and supports previous findings that FFAs lead to insulin resistance in the liver via the PKC-NFκB pathway. 2 , 3


2009 ◽  
Vol 94 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Antti P. M. Viljanen ◽  
Patricia Iozzo ◽  
Ronald Borra ◽  
Mikko Kankaanpää ◽  
Anna Karmi ◽  
...  

Abstract Objective: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity. Hypothesis: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content. Design: Thirty-four healthy obese subjects (body mass index, 33.7 ± 8.0 kg/m2) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [18F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [18F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy. Results: Subjects lost weight (11.2 ± 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05). Conclusions: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.


Metabolism ◽  
1987 ◽  
Vol 36 (5) ◽  
pp. 502-506 ◽  
Author(s):  
Stefano Bevilacqua ◽  
Riccardo Bonadonna ◽  
Giuseppe Buzzigoli ◽  
Claudio Boni ◽  
Demetrio Ciociaro ◽  
...  

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5157-5164 ◽  
Author(s):  
Thomas A. Bowman ◽  
Sadeesh K. Ramakrishnan ◽  
Meenakshi Kaw ◽  
Sang Jun Lee ◽  
Payal R. Patel ◽  
...  

Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2–3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.


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