trans-10-cis-12-conjugated-linoleic-acid and Fatty-Liver

Obesity is associated with a high risk of developing diabetes and cardiovascular disease. Therefore, management of body weight to prevent obesity remains as an important priority. The present investigation addresses the effects of conjugated linoleic acid (CLA) isomers on body weight and composition of body fat in female C57Bl/6J mice. To investigate the differential effects of individual CLA isomers and their mixture on changes in lean mass, fat mass, glucose and insulin, 6-month-old female C57BL/6J mice were fed with 10% corn oil (CO) as a dietary fat source and either supplemented with purified cis 9,trans 11 (c9t11) CLA (0.5%) or trans 10,cis 12 (t10c12) CLA (0.5%) and/or their mixture (50:50) for 6 months. As a result of 6 months' dietary intervention, both the t10c12-CLA and CLA mix showed increased lean mass and reduced fat mass compared to the CO and c9t11-CLA groups. Insulin resistance was, however, increased in t10c12-CLA and CLA mix-fed groups based on the results of homeostasis model assessment (HOMA), the revised quantitative insulin-sensitivity check index (R-QUICKI) and also with intravenous glucose tolerance test (IVGTT). In conclusion, long-term feeding of the major CLA isomers in 12-month-old C57Bl/6J mice revealed a contrasting effect on fat mass, glucose and insulin metabolism. The t10c12 isomer is found to reduce the fat mass and increase the lean mass but significantly contributed to increase insulin resistance and liver steatosis, whereas c9t11 isomer prevented the insulin resistance.

Topics: Aging; Animals; Biomarkers; Body Constitution; Corn Oil; Dietary Fats, Unsaturated; Fatty Liver; Female; Glucose Intolerance; Hypertriglyceridemia; Inflammation Mediators; Insulin Resistance; Isomerism; Linoleic Acids, Conjugated; Mice; Mice, Inbred C57BL; Obesity; Sarcopenia; Time Factors

The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice. In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation; however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days. Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of .01, and 775 were considered significant using a false discovery rate (FDR) threshold of .05. While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4alpha, a transcription factor important in controlling liver metabolic status.

Topics: Animals; Fatty Liver; Gene Expression Profiling; Hepatocyte Nuclear Factor 4; Linoleic Acids, Conjugated; Liver; Male; Mice; Obesity

Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.

Topics: Adipose Tissue, White; Animals; Dietary Fats; Dietary Supplements; Erythrocytes; Fatty Liver; Female; Humans; Linoleic Acids, Conjugated; Lipid Metabolism; Lipodystrophy; Liver; Mice; Mice, Inbred BALB C; Random Allocation; Stearoyl-CoA Desaturase

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are found in 35 and 30 % of US adults, respectively. Trans-10, cis-12-conjugated linoleic acid (CLA) has been found to cause both these disorders in several animal models. We hypothesised that IR and NAFLD caused by CLA result from n-3 fatty acid deficiency. Pathogen-free C57BL/6N female mice (aged 8 weeks; n 10) were fed either a control diet or diets containing trans-10, cis-12-CLA (0.5 %) or CLA+flaxseed oil (FSO) (0.5 %+0.5 %) for 8 weeks. Weights of livers, concentration of circulating insulin, values of homeostatic model 1 (HOMA1) for IR and HOMA1 for beta cell function were higher by 160, 636, 985 and 968 % in the CLA group compared with those in the control group. FSO decreased fasting glucose by 20 % and liver weights by 37 % compared with those in the CLA group; it maintained circulating insulin, HOMA1-IR and HOMA1 for beta cell function at levels found in the control group. CLA supplementation decreased n-6 and n-3 wt% concentrations of liver lipids by 57 and 73 % and increased the n-6:n-3 ratio by 58 % compared with corresponding values in the control group. FSO increased n-6 and n-3 PUFA in liver lipids by 33 and 342 % and decreased the n-6:n-3 ratio by 70 % compared with corresponding values in the CLA group. The present results suggest that some adverse effects of CLA may be due to n-3 PUFA deficiency and that these can be corrected by a concomitant increase in the intake of alpha-linolenic acid, 18 : 3n-3.

Topics: Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Body Weight; Disease Models, Animal; Eating; Fatty Liver; Female; Insulin; Insulin Resistance; Linoleic Acids, Conjugated; Linseed Oil; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Organ Size

To study the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on liver size and composition, as well as on hepatic lipogenesis and fatty acid oxidation, in adult hamsters.. Sixteen male Syrian Golden hamsters (8-month-old; initial body weight 167 +/- 5 g) were divided into two groups and fed on atherogenic diets supplemented either with 0.5% linoleic acid or trans-10,cis-12 CLA, for 6 weeks. Liver lipids, fatty acid profile, protein, water and DNA contents were analysed. The activity and expression of several enzymes involved in liver fatty oxidation and lipogenesis were assessed, as was the expression of transcriptional factors controlling these enzymes.. The addition of CLA to the diet led to significantly greater liver weight due to hyperplasia. No changes were observed in liver composition. CLA did not modify the expression or the activity of analysed oxidative enzymes. With regard to lipogenic enzymes, an increase in the expression and the activity of acetyl-CoA carboxylase was found.. These results show that the expected body fat-lowering effect of trans-10,cis-12 CLA, observed in young rodents, is not found in adult hamsters. The lack of increase in liver fatty acid oxidation, help to explain why that effect was not found in these animals. Further, the CLA treatment-induced hepatomegaly is a consequence of hyperplasia.

Topics: Acetyl-CoA Carboxylase; Age Factors; Animals; Cricetinae; Diet, Atherogenic; Dietary Fats; Fatty Liver; Hepatomegaly; Hyperplasia; Linoleic Acid; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Mesocricetus; Organ Size; Oxidoreductases

Mice fed diets containing trans 10, cis 12 (t10, c12)-conjugated linoleic acid (CLA) develop fatty livers and the role of the hepatic fatty acid oxidation enzymes in this development is not well defined. We examined the effects of dietary cis 9, trans 11-CLA (c9, t11-CLA) and t10, c12-CLA on the expression of hepatic genes for fatty acid metabolism. Female mice, 8 weeks old, (six animals per group) were fed either a control diet or diets supplemented with 0.5% c9, t11- or c12-CLA for 8 weeks. DNA microarray analysis showed that t10, c12-CLA increased the expression of 278 hepatic genes and decreased those of 121 genes (>2 fold); c9, t11-CLA increased expression of twenty-two genes and decreased those of nine. Real-time PCR confirmed that t10, c12-CLA reduced by the expression of fatty acid oxidation genes including flavin monooxygenase (FMO)-3 95%, cytochrome P450 (cyt p450) 69%, carnitine palmitoyl transferase 1a 77%, acetyl CoA oxidase (ACOX) 50% and PPARalpha 65%: it increased the expression of fatty acid synthase by 3.5-fold (P<0.05 for all genes, except ACOX P=0.08). It also reduced the enzymatic activity of hepatic microsomal FMO by 40% and the FMO3 specific protein by 67%. c9, t11-CLA reduced FMO3 and cyt P450 expression by 61% (P=0.001) and 38% (P=0.06) and increased steoryl CoA desaturase transcription by 5.9-fold (P=0.07). Both decreased fatty acid oxidation and increased fatty acid synthesis seem to contribute to the CLA-induced fatty liver. Since FMO and cyt P450 are also involved in drug detoxification, suppression of the transcription of these genes by CLA may have other health consequences besides development of fatty liver.

Topics: Animal Feed; Animals; Base Sequence; Blotting, Western; DNA Primers; Fatty Acids; Fatty Liver; Female; Gene Expression Profiling; Immunoprecipitation; Inactivation, Metabolic; Linoleic Acids, Conjugated; Liver; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Oxidation-Reduction; Oxygenases; Reverse Transcriptase Polymerase Chain Reaction