Objective Current data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake. Methods To address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes). Results Here, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure—likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3-HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling. Conclusion These data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.

Purpose The purpose of this review is to give an overview on recently published articles investigating the associations of diet and dietary interventions with biomarkers of oxidative stress with special emphasis on different categories of redox biomarkers. Findings Intervention and observational studies both in healthy participants and patients that investigated associations of dietary habits, foodstuffs or isolated nutrients with biomarkers of oxidative stress were included in this review. Recently published observation studies confirm the inverse association between fruit and vegetable intake and oxidative stress markers. Studies investigating the effect of vitamin D and vitamin E, magnesium, zinc, chromium, selenium, probiotic supplementation and several phytochemicals reported consistent changes in redox biomarkers. Of 88 articles included in this review, only seven studies measured biomarkers from the three categories: oxidative damage, endogenous antioxidants, and exogenous antioxidants. Many studies rely on controversial assays for total antioxidant capacity, thus there is potential in many studies to improve biomarker repertoire to cover all three categories of biomarkers and to turn away from such assays.

Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to investigate whether and to which extent plasma status of micronutrients, amino acids, phospholipids and oxidative stress differs between morbidly obese (n = 23) and non-obese patients (n = 13). In addition to plasma, malondialdehyde, retinol, cholesterol and triglycerides were assessed in visceral and subcutaneous adipose tissue in both groups. Plasma γ-tocopherol was significantly lower (p < 0.011) in the obese group while other fat-soluble micronutrients showed no statistically significant differences between both groups. Branched-chain amino acids (all p < 0.008) and lysine (p < 0.006) were significantly higher in morbidly obese patients compared to the control group. Malondialdehyde concentrations in both visceral (p < 0.016) and subcutaneous (p < 0.002) adipose tissue were significantly higher in the morbidly obese group while plasma markers of oxidative stress showed no significant differences between both groups. Significantly lower plasma concentrations of phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine (all p < 0.05) and their corresponding ether-linked analogs were observed, which were all reduced in obese participants compared to the control group. Pre-operative assessment of micronutrients in patients undergoing bariatric surgery is recommended for early identification of patients who might be at higher risk to develop a severe micronutrient deficiency post-surgery. Assessment of plasma BCAAs and phospholipids in obese patients might help to differentiate between metabolic healthy patients and those with metabolic disorders.