Thiazolidinedione Treatment Prevents Free Fatty Acid-Induced Insulin Resistance in Male Wistar Rats

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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Variants in the Calpain-10 Gene Predispose to Insulin Resistance and Elevated Free Fatty Acid Levels

Diabetes ◽

10.2337/diabetes.51.8.2658 ◽

2002 ◽

Vol 51 (8) ◽

pp. 2658-2664 ◽

Cited By ~ 84

Author(s):

M. Orho-Melander ◽

M. Klannemark ◽

M. K. Svensson ◽

M. Ridderstrale ◽

C. M. Lindgren ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Free Fatty Acid ◽

Calpain 10

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Effects of Cyclic Fatty Acid Monomers from Heated Vegetable Oil on Markers of Inflammation and Oxidative Stress in Male Wistar Rats

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.8b01836 ◽

2018 ◽

Vol 66 (27) ◽

pp. 7172-7180 ◽

Cited By ~ 6

Author(s):

Jean Mboma ◽

Nadine Leblanc ◽

Paul Angers ◽

Amandine Rocher ◽

Claire Vigor ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Vegetable Oil ◽

Wistar Rats ◽

Cyclic Fatty Acid ◽

Cyclic Fatty Acid Monomers ◽

Markers Of Inflammation ◽

Male Wistar Rats ◽

And Oxidative Stress

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Article Commentary: A Role for IR-β in the Free Fatty Acid Mediated Development of Hepatic Insulin Resistance?

Biochemistry Insights ◽

10.4137/bci.s2996 ◽

2009 ◽

Vol 2 ◽

pp. BCI.S2996

Author(s):

Samit Shah ◽

Arthur G. Cox

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acid ◽

Free Fatty Acids ◽

Pi3k Pathway ◽

Hepatic Insulin Resistance ◽

Hamster Model ◽

High Concentrations ◽

Nfκb Pathway

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

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Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2011-1884 ◽

2012 ◽

Vol 97 (1) ◽

pp. 208-216 ◽

Cited By ~ 19

Author(s):

Joris Hoeks ◽

Marco Mensink ◽

Matthijs K. C. Hesselink ◽

Kim Ekroos ◽

Patrick Schrauwen

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fat Accumulation ◽

Medium Chain ◽

Medium Chain Fatty Acids ◽

Induce Insulin Resistance ◽

Chain Fatty Acids

Context: Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling. Objective: We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance. Design and Methods: Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp. Results: MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (−28%, P = 0.003) and MCT/LCT (−20%, P < 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered. Conclusions: Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.

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Palmitate Induced Mitochondrial Deoxyribonucleic Acid Damage and Apoptosis in L6 Rat Skeletal Muscle Cells

Endocrinology ◽

10.1210/en.2006-0998 ◽

2007 ◽

Vol 148 (1) ◽

pp. 293-299 ◽

Cited By ~ 93

Author(s):

L. I. Rachek ◽

S. I. Musiyenko ◽

S. P. LeDoux ◽

G. L. Wilson

Keyword(s):

Insulin Resistance ◽

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Fatty Acid ◽

Free Fatty Acid ◽

Mitochondrial Dysfunction ◽

No Synthase ◽

Oxygen Species ◽

Mtdna Damage ◽

L6 Myotubes

A major characteristic of type 2 diabetes mellitus (T2DM) is insulin resistance in skeletal muscle. A growing body of evidence indicates that oxidative stress that results from increased production of reactive oxygen species and/or reactive nitrogen species leads to insulin resistance, tissue damage, and other complications observed in T2DM. It has been suggested that muscular free fatty acid accumulation might be responsible for the mitochondrial dysfunction and insulin resistance seen in T2DM, although the mechanisms by which increased levels of free fatty acid lead to insulin resistance are not well understood. To help resolve this situation, we report that saturated fatty acid palmitate stimulated the expression of inducible nitric oxide (NO) synthase and the production of reactive oxygen species and NO in L6 myotubes. Additionally, palmitate caused a significant dose-dependent increase in mitochondrial DNA (mtDNA) damage and a subsequent decrease in L6 myotube viability and ATP levels at concentrations as low as 0.5 mm. Furthermore, palmitate induced apoptosis, which was detected by DNA fragmentation, caspase-3 cleavage, and cytochrome c release. N-acetyl cysteine, a precursor compound for glutathione formation, aminoguanidine, an inducible NO synthase inhibitor, and 5,10,15,20-tetrakis(4-sulphonatophenyl) porphyrinato iron (III), a peroxynitrite inhibitor, all prevented palmitate-induced mtDNA damage and diminished palmitate-induced cytotoxicity. We conclude that exposure of L6 myotubes to palmitate induced mtDNA damage and triggered mitochondrial dysfunction, which caused apoptosis. Additionally, our findings indicate that palmitate-induced mtDNA damage and cytotoxicity in skeletal muscle cells were caused by overproduction of peroxynitrite.

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