Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids

2014 ◽  
Vol 31 (5) ◽  
pp. 453-475 ◽  
Author(s):  
Mohamad Hafizi Abu Bakar ◽  
Cheng Kian Kai ◽  
Wan Najihah Wan Hassan ◽  
Mohamad Roji Sarmidi ◽  
Harisun Yaakob ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance

2011 ◽  
Vol 22 (4) ◽  
pp. 366-371 ◽  
Author(s):  
Johan De Vogel-van den Bosch ◽  
Sjoerd A.A. van den Berg ◽  
Silvia Bijland ◽  
Peter J. Voshol ◽  
Louis M. Havekes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Long Chain Fatty Acids ◽  
High Fat ◽  
Tissue Specific ◽  
High Fat Diets ◽  
Fat Diets ◽  
Specific Insulin ◽  
Long Chain ◽  
Chain Fatty Acids

Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

2000 ◽  
Vol 279 (6) ◽  
pp. E1286-E1293 ◽  
Author(s):  
Lambertus Benthem ◽  
Klaasjan Keizer ◽  
Coen H. Wiegman ◽  
Sietse F. de Boer ◽  
Jan H. Strubbe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Hpa Axis ◽  
Chain Fatty Acid ◽  
Sympathetic System ◽  
Long Chain Fatty Acids ◽  
Intravenous Glucose ◽  
Long Chain ◽  
Chain Fatty Acids

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the long-chain fatty acid oleate (150 nmol/min, 24 h), the medium-chain fatty acid caprylate, or the solvent. Corticosterone (Cort) and norepinephrine (NE) were measured as indexes for HPA axis and sympathetic activity, respectively. Insulin sensitivity was assessed by means of an intravenous glucose tolerance test (IVGTT). Oleate infusion induced increases in plasma Cort (Δ = 13.5 ± 3.6 μg/dl; P < 0.05) and NE (Δ = 235 ± 76 ng/l; P < 0.05), whereas caprylate and solvent had no effect. The area under the insulin response curve to the IVGTT was larger in the oleate-treated group than in the caprylate and solvent groups (area = 220 ± 35 vs. 112 ± 13 and 106 ± 8, respectively, P < 0.05). The area under the glucose response curves was comparable [area = 121 ± 13 (oleate) vs. 135 ± 20 (caprylate) and 96 ± 11 (solvent)]. The results are consistent with the concept that increased portal free fatty acid is involved in the induction of visceral obesity-related insulin resistance via activation of the HPA axis and sympathetic system.

scholarly journals Increased Accumulation of Long‐chain Fatty Acids in Skeletal Muscle May Contribute Insulin Resistance in Znt7 Knockout Mice

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Surapun Tepaamorndech ◽  
Catherine Kirschke ◽  
Theresa Pedersen ◽  
William Keyes ◽  
John Newman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Knockout Mice ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1826
Author(s):  
Jie Zhou ◽  
Marcia R. Terluk ◽  
Paul J. Orchard ◽  
James C. Cloyd ◽  
Reena V. Kartha
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Specific Effects ◽  
Low Concentrations ◽  
Long Chain ◽  
Chain Fatty Acids

The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.

scholarly journals Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Liver Injury ◽  
Olive Oil ◽  
Coconut Oil ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons &lt; 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

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