Mixed conjugated linoleic acid sex‐dependently reverses high‐fat diet‐induced insulin resistance via the gut‐adipose axis

The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (Rmax=53±4.7 %; pEC50=6±0.2) compared to endothelium-intact aortas (Rmax=100±9.9 %; pEC50=7±0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endothelium-independent vasodilatation before the onset of HFD-induced insulin resistance.

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Antiobesity effect of PEGylated conjugated linoleic acid on high-fat diet-induced obese C57BL/6J (ob/ob) mice: attenuation of insulin resistance and enhancement of antioxidant defenses

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2008.02.001 ◽

2009 ◽

Vol 20 (3) ◽

pp. 187-194 ◽

Cited By ~ 16

Author(s):

Hyun-Seuk Moon ◽

Hong-Gu Lee ◽

Ji-Hye Seo ◽

Chung-Soo Chung ◽

Tae-Gyu Kim ◽

...

Keyword(s):

Insulin Resistance ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

High Fat Diet ◽

Antioxidant Defenses ◽

High Fat

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High Dose of A Conjugated Linoleic Acid Mixture Increases Insulin Resistance in Rats Fed Either A Low Fat or A High Fat Diet

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-118348 ◽

2018 ◽

Vol 126 (06) ◽

pp. 379-386 ◽

Cited By ~ 7

Author(s):

Priscila Bezan ◽

Héric Holland ◽

Gabriela de Castro ◽

João Cardoso ◽

Paula Ovidio ◽

...

Keyword(s):

Insulin Resistance ◽

Linoleic Acid ◽

Soybean Oil ◽

Conjugated Linoleic Acid ◽

Fat Mass ◽

High Fat Diet ◽

High Dose ◽

High Fat ◽

Low Fat ◽

Animal Fat

AbstractObesity and related diseases are becoming more prevalent. Conjugated linoleic acid (CLA) might be a useful coadjutant treatment helping to decrease fat mass. However, the precise impact of CLA is unclear because the decreased body fat mass is followed by an increase in insulin resistance. This study aimed to evaluate some of the consequences of a high dose of CLA in rats fed a normal low fat or a high fat diet for 30 days. Male Wistar rats were separated into 4 groups (each n = 10): Control group receiving 7% fat (soybean oil); CLA group receiving 4% soybean oil and 3% CLA mixture; animal fat (AF) group, receiving 45% fat (lard); and animal fat plus CLA (AF+CLA) group, receiving 42% lard and 3% CLA mixture. The CLA mixture contained 39.32 mole% c9,t11-CLA and 40.50 mole% t10,c12-CLA. After 30 days, both CLA groups (CLA and AF+CLA groups) developed insulin resistance, with an increase in glucose in the fasting state and in an insulin tolerance test. The CLA group had increased liver weight and percentage of saturated fatty acids in liver and adipose tissue. Feeding the high fat diet resulted in increased hepatic triacylglycerol accumulation and this was exacerbated by dietary CLA. It is concluded that a high dose of CLA mixture increases insulin resistance and exacerbates hepatic steatosis when combined with a high fat diet.

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Effects of three different conjugated linoleic acid preparations on insulin signalling, fat oxidation and mitochondrial function in rats fed a high-fat diet

British Journal Of Nutrition ◽

10.1017/s000711450770497x ◽

2007 ◽

Vol 98 (2) ◽

pp. 264-275 ◽

Cited By ~ 35

Author(s):

Joo Sun Choi ◽

In-Uk Koh ◽

Myeong Ho Jung ◽

Jihyun Song

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Linoleic Acid ◽

Mitochondrial Function ◽

High Fat Diet ◽

Insulin Signalling ◽

Fat Oxidation ◽

Acid Oxidation ◽

High Fat ◽

Cla Isomers

To investigate the effects of three different conjugated linoleic acid (CLA) preparations containing different ratios of CLA isomers on insulin signalling, fatty acid oxidation and mitochondrial function, Sprague–Dawley rats were fed a high-fat diet either unsupplemented or supplemented with one of three CLA preparations at 1 % of the diet for 8 weeks. The first CLA preparation contained approximately 30 % cis-9, trans-11 (c9, t11)-CLA isomer and 40 % trans-10, cis-12 (t10, c12)-CLA isomer (CLA-mix). The other two preparations were an 80:20 mix (c9, t11-CLA-mix) or a 10:90 mix of two CLA isomers (t10, c12-CLA-mix). Insulin resistance was decreased in all three supplemented groups based on the results of homeostasis model assessment and the revised quantitative insulin-sensitivity check index. The phosphorylation of insulin receptor substrate-1 on serine decreased in the livers of all three supplemented groups, while subsequent Akt phosphorylation increased only in the t10, c12-CLA-mix group. Both the c9, t11-CLA-mix and the t10, c12-CLA-mix increased the expression of hepatic adiponectin receptors R1 and 2, which are thought to enhance insulin sensitivity and fat oxidation. The c9, t11-CLA-mix increased protein and mRNA levels of PPARα, acyl-CoA oxidase and uncoupling protein, which are involved in fatty acid oxidation and energy dissipation. The c9, t11-CLA-mix enhanced mitochondrial function and protection against oxidative stress by increasing the activities of cytochrome c oxidase, manganese-superoxide dismutase, glutathione peroxidase, and glutathione reductase and the level of GSH. In conclusion, all three CLA preparations reduced insulin resistance. Among them, the c9, t11-CLA-mix was the most effective based on the parameters reflecting insulin resistance and fat oxidation, and mitochondrial antioxidative enzyme activity in the liver.

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