Long-Term Effects of Dietary Protein and Branched-Chain Amino Acids on Metabolism and Inflammation in Mice.

Aging is the main factor involved in the onset of degenerative diseases. Dietary protein restriction has been shown to increase the lifespan of rodents and improve metabolic phenotype. Branched-chain amino acids (BCAA) can act as nutrient signals that increase the lifespan of mice after prolonged supplementation. It remains unclear whether the combination of protein restriction and BCAA supplementation improves metabolic and immunological profiles during aging. Here, we investigated how dietary protein levels and BCAA supplementation impact metabolism and immune profile during a 12-month intervention in adult male C57BL/6J mice. We found that protein restriction improved insulin tolerance and increased hepatic fibroblast growth factor 21 mRNA, circulating interleukin (IL)-5 concentration, and thermogenic uncoupling protein 1 in subcutaneous white fat. Surprisingly, BCAA supplementation conditionally increased body weight, lean mass, and fat mass, and deteriorated insulin intolerance during protein restriction, but not during protein sufficiency. BCAA also induced pro-inflammatory gene expression in visceral adipose tissue under both normal and low protein conditions. These results suggest that dietary protein levels and BCAA supplementation coordinate a complex regulation of metabolism and tissue inflammation during prolonged feeding.

Blueberries improve glucose tolerance without altering body composition in obese postmenopausal mice.

OBJECTIVE: Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated postmenopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, the effects of BB supplementation on obese postmenopausal mice using a chemically induced menopause model were examined. METHODS: After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. RESULTS: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation. CONCLUSIONS: BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and these effects are independent of body weight.

A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.

OBJECTIVE AND BACKGROUND: To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the highest antioxidant capacities of fruits and vegetables. METHODS AND RESULTS: Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS), peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver) assayed in BB-fed rats. These results were evidence of "hormesis" during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group. CONCLUSION: Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated the potential to delay or attenuate development of hypertension-induced renal injury, and these effects appear to be mediated by a short-term hormetic response.