Inter-organ proteomic analysis reveals insights into the molecular mechanisms underlying the anti-diabetic effects of cis-9, trans-11-conjugated linoleic acid in ob/ob mice.

cis-9, trans-11-Conjugated linoleic acid (c9 t11 CLA) exerts anti-diabetic effects by improving systemic insulin sensitivity and inflammation. Levels of CLA in beef can be increased by feeding cattle on pasture. This study aimed to explore the efficacy of a CLA-rich diet (0.6% w/w c9 t11 CLA), presented as beef enriched with CLA or beef supplemented with synthetic CLA (c9 t11 CLA), for 28 days on molecular biomarkers of the metabolic syndrome, and adipose, hepatic, and skeletal muscle proteome in male ob/ob mice. Despite equal weight gain, CLA-fed mice had lower plasma glucose, insulin, non-esterified fatty acid, triacylglycerol and interleukin-6, and higher adiponectin concentrations than controls. c9 t11 CLA induced differential regulation of redox status across all tissues, and decreased hepatic and muscle endoplasmic reticulum stress. CLA also modulated mechanistic links between the actin cytoskeleton, insulin signalling, glucose transport and inflammation in the adipose tissue. In the liver and muscle, c9 t11 CLA improved metabolic flexibility through co-ordination between carbohydrate and energy metabolism. c9 t11 CLA may ameliorate systemic insulin sensitivity in obesity-induced diabetes by altering cellular stress and redox status, and modulating nutrient handling in key insulin-sensitive tissues through complex biochemical interplay among representative proteomic signatures.

Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention.

Obesity frequently leads to insulin resistance and the development of hepatic steatosis. To characterize the molecular changes that promote hepatic steatosis, transcriptomics, proteomics, and metabolomics technologies were applied to liver samples from C57BL/6J mice obtained from two independent intervention trials. After 12 wk of high-fat feeding the animals became obese, hyperglycemic, and insulin resistant, had elevated levels of blood cholesterol and VLDL, and developed hepatic steatosis. Nutrigenomic analysis revealed alterations of key metabolites and enzyme transcript levels of hepatic one-carbon metabolism and related pathways. The hepatic oxidative capacity and the lipid milieu were significantly altered, which may play a key role in the development of insulin resistance. Additionally, high choline levels were observed after the high-fat diet. Previous studies have linked choline levels with insulin resistance and hepatic steatosis in conjunction with changes of certain metabolites and enzyme levels of one-carbon metabolism. The present results suggest that the coupling of high levels of choline and low levels of methionine plays an important role in the development of insulin resistance and liver steatosis. In conclusion, the complexities of the alterations induced by high-fat feeding are multifactorial, indicating that the interplay between several metabolic pathways is responsible for the pathological consequences.