trans-10-cis-12-conjugated-linoleic-acid and Obesity

Hyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies, but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time. As trans10cis12 (t10c12)-conjugated linoleic acid (CLA) supplementation induces insulin resistance in obese men, we used this fatty acid to investigate the effects on plasma proinsulin, insulin, C-peptide and adiponectin concentrations, including their associations with change in insulin sensitivity.. We randomised (double-blind) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA, CLA-isomer mixture or control oil for 12 weeks. Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), intact proinsulin, insulin, the proinsulin : insulin ratio, C-peptide, glucose and adiponectin were assessed before and after supplementation.. Supplementation with t10c12CLA increased proinsulin (p<0.01), the proinsulin : insulin ratio (p<0.05) and C-peptide concentrations (p<0.001) in comparison with control subjects. Adiponectin, however, did not change significantly. The change in proinsulin, but not the proinsulin : insulin ratio, was related to impaired insulin sensitivity (r= -0.58, p<0.0001), independently of changes in insulin, C-peptide, glucose, adiponectin and BMI. Conversely, the correlation between insulin sensitivity and specific insulin (r=-0.46, p<0.001) did not remain significant after adjustment for proinsulin. Induced hyperproinsulinaemia was also correlated to adiponectin concentrations ( r= -0.34, p<0.01).. In obese men, t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity, independently of changes in insulin concentrations. These results are of clinical interest, as hyperproinsulinaemia predicts diabetes and cardiovascular disease. The use of weight-loss supplements containing this fatty acid is worrying.

Topics: Abdomen; Adiponectin; Adipose Tissue; Analysis of Variance; Blood Glucose; C-Peptide; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Humans; Hyperinsulinism; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Linoleic Acids, Conjugated; Male; Obesity; Time Factors

Caloric restriction (CR) is one of the most promising strategies for weight loss but is associated with loss of lean mass, whereas compounds such as trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) have been promoted as antiobesity agents. To compare the mechanisms of weight reduction by CR and t10-c12 CLA, body composition, glucose control, and characteristics of adipose tissue with respect to cell turnover (stem cells and preadipocytes, apoptosis and autophagy) and Tbx-1 localization were examined in obese db/db mice and lean C57BL/6J mice undergoing CR or fed CLA isomers (0.4% w/w c9-t11 or t10-c12) for 4 weeks. Our findings show that the t10-c12 CLA reduced whole-body fat mass by decreasing all fat depots (visceral, inguinal, brown/interscapular), while CR lowered both whole-body fat and lean mass in obese mice. t10-c12 CLA elevated blood glucose in both obese and lean mice, while glycemia was not altered by CR. The adipocyte stem cell population remained unchanged; however, t10-c12 CLA reduced and CR elevated the proportion of immature adipocytes in obese mice, suggesting differential effects on adipocyte maturation. t10-c12 CLA reduced apoptosis (activated caspase-3) in both obese and lean mice but did not alter autophagy (LC3II/LC3I). Nuclear Tbx-1, a marker of metabolically active beige adipocytes, was greater in the adipose of t10-c12 CLA-fed animals. Thus, weight loss achieved via t10-c12 CLA primarily involves fat loss and more cells with Tbx-1 localized to the nucleus, while CR operates through a mechanism that reduces both lean and fat mass and blocks adipocyte differentiation.

Topics: Adipogenesis; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Adult Stem Cells; Animals; Anti-Obesity Agents; Apoptosis; Biomarkers; Caloric Restriction; Dietary Supplements; Linoleic Acids, Conjugated; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Random Allocation; T-Box Domain Proteins; Weight Loss

Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B₂. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Cyclooxygenase 1; Dietary Supplements; Disease Progression; Fibrosis; Hypertrophy; Kidney; Linoleic Acids, Conjugated; Macrophage Activation; Membrane Proteins; Obesity; Oxylipins; Rats, Zucker; Renal Insufficiency; Severity of Illness Index; Thromboxane B2

The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non-conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Δ9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation.

Topics: Adipose Tissue; Animals; Body Composition; Chromatography, High Pressure Liquid; Dietary Fats; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Muscles; Obesity; Palm Oil; Plant Oils; Rats; Rats, Zucker; Sheep, Domestic; Stearoyl-CoA Desaturase

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

Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2 % cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1 % of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-alpha and IL-1beta. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition.

Topics: Adipokines; Adipose Tissue; Animals; Body Composition; Cholesterol; Dietary Fats; Dietary Fats, Unsaturated; Epididymis; Fatty Acids; Intra-Abdominal Fat; Linoleic Acids, Conjugated; Lipids; Liver; Male; Obesity; Organ Size; Palm Oil; Plant Oils; Plasminogen Activator Inhibitor 1; Rats; Rats, Zucker; Sheep

Conjugated linoleic acid (CLA) has shown a number of biologically beneficial effects, including prevention of obesity. The purpose of this study was to test effects of dietary supplementation of 0.5% trans-10,cis-12 CLA in a high fat diet in neuronal basic helix-loop-helix 2 knock-out animals (N2KO), which is a unique animal model representing adult-onset inactivity-related obesity. Eight wild-type (WT) and eight N2KO female mice were fed either 0.5% trans-10,cis-12 CLA-containing diet or control diet (with 20% soybean oil diet) for 12 weeks. Body weights, food intake, adipose tissue weights, body compositions, and blood parameters were analyzed. Overall, N2KO animals had greater body weights, food intake, adipose tissue weights, and body fat compared to WT animals. CLA supplementation decreased overall body weights and total fat, and the effect of dietary CLA on adipose tissue reduction was greater in N2KO than in WT mice. Serum leptin and triglyceride levels were reduced by CLA in both N2KO and WT animals compared to control animals, while there was no effect by CLA on serum cholesterol. The effect of CLA to lower fat mass, increase lean body mass, and lower serum leptin and triglycerides in sedentary mice supports the possibility of using CLA to prevent or alleviate ailments associated with obesity.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Dietary Supplements; Energy Intake; Female; Leptin; Linoleic Acids, Conjugated; Mice; Mice, Knockout; Mice, Obese; Obesity; Triglycerides

Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and beneficially affect glucose metabolism in animals, but the results are inconsistent and seem to depend on animal model and type of CLA isomer. In the present study, feeding male Zucker fa/fa rats diets supplemented with 1% trans-10, cis-12-CLA for 10 d reduced the liver TAG content without improving the overall adiposity, and enhanced hepatic mitochondrial and peroxisomal beta-oxidation. The increased carnitine palmitoyltransferase (CPT)-I activity and mRNA level as well as the increased n-3:n-6 PUFA ratio in liver suggest that trans-10, cis-12-CLA increased the hepatic beta-oxidation by stimulation of PPARalpha. The reduced hepatic TAG content may be partly due to lower activity of stearoyl-CoA desaturase, as the ratios of 18 : 1n-9:18 : 0 and 16 : 1n-7:16 : 0 were reduced in liver. Trans-10, cis-12-CLA increased the CPT-I mRNA in retroperitoneal white adipose tissue (WAT), and increased uncoupling protein-2 mRNA in epididymal and inguinal WAT depots. Leptin mRNA level was decreased in all examined WAT depots, implying reduced insulin sensitivity. The resistin mRNA level was increased in all WAT depots, whereas adiponectin mRNA was reduced in inguinal and retroperitoneal WAT. The present results suggest that dietary supplementation with trans-10, cis-12-CLA may increase the catabolism of lipids in liver and adipose tissue. Moreover, we provide new data suggesting that trans-10, cis-12-CLA modulates the expression of resistin and adiponectin inversely in adipose tissue. Hence, the present results suggest that trans-10, cis-12-CLA may have some beneficial effects on lipid metabolism and adiposity but possibly reduces insulin sensitivity.

Topics: Adipokines; Adipose Tissue; Animals; Carnitine O-Palmitoyltransferase; Dietary Supplements; Disease Models, Animal; Fatty Acids; Growth; Ion Channels; Leptin; Linoleic Acids, Conjugated; Lipid Metabolism; Liver; Male; Mitochondrial Proteins; Obesity; Organ Size; Rats; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Triglycerides; Uncoupling Protein 2

To observe the antiobesity activity of trans-10,cis-12-conjugated linoleic acid (CLA)-producing lactobacillus in mice.. Lactobacillus plantarum PL62, which can grow in the presence of linoleic acid, was selected and studied. The culture supernatant of Lact. plantarum PL62 contained trans-10,cis-12-conjugated linoleic acid (6.4 microg ml(-1)), and the crude enzyme prepared from washed cells produced trans-10,cis-12 CLA (1395 microg mg(-1) protein). Lact. plantarum PL62 reduced the weights of epididymal, inguinal, mesenteric, and perirenal white adipose tissues and significantly reduced the blood levels of total glucose and body weights of mice (P<0.01).. trans-10,cis-12-CLA-producing Lact. plantarum PL62 can exert the same antiobesity activity as trans-10,cis-12-CLA in mice.. trans-10,cis-12-CLA-producing Lactobacillus can be a replacement for CLA for obesity treatment via the continuous production of trans-10,cis-12-CLA. The results provide a novel opportunity to develop foods with antiobesity activity.

Topics: Animals; Chromatography, Gas; Dietary Fats; Eating; Energy Intake; Feces; Glycerol; Lactobacillus plantarum; Leptin; Linoleic Acids, Conjugated; Lipids; Male; Mice; Mice, Inbred C57BL; Obesity; Organ Size; Probiotics; Weight Gain

Growing female obese Zucker (fa/fa) rats were treated (via intragastric gavage) for 21 d with either a (i) vehicle [corn oil; 0.9 g/kg body weight (BW)], (ii) CLA mixture [50:50; trans-10, cis-12 and cis-9, trans-11 CLA], (iii) cis-9,trans-11 CLA, or (iv) trans- 10, cis-12 CLA (CLA treatments at 1.5 g CLA/kg BW). Compared with controls, average daily gain (g/d) was reduced 24 and 44% by the CLA mixture and trans-10, cis-12 CLA, respectively. There was no treatment effect on average whole-body (minus heart and liver) composition (dry matter basis): fat (70.2%), protein (21.0%), and ash (4.3%). Compared with animals treated with cis-9,trans-11 CLA, obese Zucker rats treated with trans-10, cis-12 and the CLA mixture had 7.8% more carcass water. Treatment had no effect on heart or liver weights or on heart or liver weights as a percentage of body weight, but compared with the other treatments trans-10, cis-12 CLA increased liver lipid content by 33%. Hepatic lipid ratios of 16:1/16:0 and 18:1/18:0 (a proxy for delta9-desaturase capability) were not affected by treatment (0.1 and 0.6, respectively). Similar to previous reports, CLA increased hepatic lipid content and altered both liver and carcass FA composition (i.e., reduced arachidonic acid content), but the ability of CLA to manipulate body composition in obese Zucker rats remains questionable.

Topics: Adipose Tissue; Animals; Body Composition; Diet; Fatty Acids; Female; Growth; Isomerism; Linoleic Acids, Conjugated; Obesity; Organ Size; Rats; Rats, Zucker