scholarly journals Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

1984 ◽  
Vol 246 (6) ◽  
pp. R1011-R1014
Author(s):  
M. J. Azain ◽  
R. J. Martin

Hepatocytes were isolated from 48-h fasted lean and obese Zucker rats and incubated with [1–14C] palmitate. The partitioning of fatty acids to oxidation and esterification products and the effect of lactate or glucose on this partitioning were studied. With palmitate as the only substrate, the cells from the lean rats oxidized 80% of the palmitate that was metabolized compared with only 35% oxidation in the cells from the obese rats. Thus fatty acid esterification remained the predominate pathway of palmitate metabolism in the hepatocytes from fasting obese rats. The addition of lactate to the cells from the lean rats decreased oxidation and increased esterification to levels similar to those in the obese rat hepatocytes. Glucose had similar effects on esterification in lean rat hepatocytes but was less potent than lactate. The cells from the obese rats were insensitive to the addition of lactate or glucose. These studies indicate that the inability of hepatocytes from obese rats to induce ketogenesis from exogenous fatty acids after a 48-h fast and their insensitivity to added lactate or glucose may be related to the availability of endogenous energy sources in the obese liver that can be oxidized and thus inhibit ketogenesis and support fatty acid esterification.


2015 ◽  
Vol 308 (4) ◽  
pp. C297-C307 ◽  
Author(s):  
Veronika Franekova ◽  
Yeliz Angin ◽  
Nicole T. H. Hoebers ◽  
Will A. Coumans ◽  
Peter J. Simons ◽  
...  

Insulin resistance is an important risk factor for the development of several cardiac pathologies, thus advocating strategies for restoring insulin sensitivity of the heart in these conditions. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), have been shown to improve insulin sensitivity in insulin-sensitive tissues, but their direct effect on insulin signaling and metabolic parameters in the myocardium has not been reported previously. The aim of this study was therefore to examine the ability of EPA and DHA to prevent insulin resistance in isolated rat cardiomyocytes. Primary rat cardiomyocytes were made insulin resistant by 48 h incubation in high insulin (HI) medium. Parallel incubations were supplemented by 200 μM EPA or DHA. Addition of EPA or DHA to the medium prevented the induction of insulin resistance in cardiomyocytes by preserving the phosphorylation state of key proteins in the insulin signaling cascade and by preventing persistent relocation of fatty acid transporter CD36 to the sarcolemma. Only cardiomyocytes incubated in the presence of EPA, however, exhibited improvements in glucose and fatty acid uptake and cell shortening. We conclude that ω-3 PUFAs protect metabolic and functional properties of cardiomyocytes subjected to insulin resistance-evoking conditions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ban-Hock Khor ◽  
◽  
Sharmela Sahathevan ◽  
Ayesha Sualeheen ◽  
Mohammad Syafiq Md Ali ◽  
...  

AbstractThe metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r =  − 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r =  − 0.197) and serum albumin (r =  − 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r =  − 0.168) and interleukin-6 concentrations (r =  − 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r =  − 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.


2004 ◽  
Vol 174 (2) ◽  
pp. 163-168 ◽  
Author(s):  
K. A. Powell ◽  
E. A. Deans ◽  
B. K. Speake

2018 ◽  
Vol 15 (30) ◽  
pp. 447-462
Author(s):  
M. C. de M. SOUZA ◽  
L. DI SOUZA ◽  
V. P. da S. Caldeira ◽  
A. G. D. SANTOS ◽  
B. ADILSON

With the increasing selective energy demand, fossil fuels are becoming scarce and environmentally incorrect, a viable alternative to this problem being the production of biodiesel. However, the esterification and transesterification reactions used are slow, expensive and ecologically incorrect because they produce polluting waste. Thus, it is necessary to develop techniques, reagents and equipment that make them fast, cheap and environmentally friendly. This work evaluated the performance of the thermal heating, microwave and ultrasonic methods in the esterification efficiency of oleic and stearic fatty acids via homogeneous acid catalysis. The efficiency of the reaction was certificated with the variables: time, yield and conversion and the biodiesel characterization were done with TG / DTG, FTIR and NMR. Conversions were determined by TG and 1H NMR and the yield by gravimetry. The results showed conversion with all methods with differences in the analyzed variables. The yields decrease in the microwave order (52%) conduction (33%) ultrasound (30%) for reactions with oleic acid and are practically the same (22, 22 and 20), independently of the stearic acid. Among the methods used, the most efficient is the microwave, because it has a higher yield in the case of oleic acid and reducing the reaction time.


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