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Background: Effects of high protein (HP) diets and prolonged energy restriction (ER) on integrated muscle protein kinetics have not been determined.Objective: The objective of this study was to measure protein kinetics in response to prolonged ER and HP on muscle protein synthesis (MPS; absolute rates of synthesis) and muscle protein breakdown (MPB; half-lives) for proteins across the muscle proteome.Methods: Female 6-wk-old obese Zucker rats (Leprfa+/fa+, n = 48) were randomly assigned to one of four diets for 10 wk: ad libitum-standard protein (AL-SP; 15% kcal from protein), AL-HP (35% kcal from protein), ER-SP, and ER-HP (both fed 60% feed consumed by AL-SP). During week 10, heavy/deuterated water (2H2O) was administered by intraperitoneal injection, and isotopic steady-state was maintained via 2H2O in drinking water. Rats were euthanized after 1 wk, and mixed-MPS as well as fractional replacement rate (FRR), relative concentrations, and half-lives of individual muscle proteins were quantified in the gastrocnemius. Data were analyzed using 2-factor (energy × protein) ANOVAs and 2-tailed t-tests or binomial tests as appropriate.Results: Absolute MPS was lower in ER than AL for mixed-MPS (-29.6%; P < 0.001) and MPS of most proteins measured [23/26 myofibrillar, 48/60 cytoplasmic, and 46/60 mitochondrial (P < 0.05)], corresponding with lower gastrocnemius mass in ER compared with AL (-29.4%; P < 0.001). Although mixed-muscle protein half-life was not different between groups, prolonged half-lives were observed for most individual proteins in HP compared with SP in ER and AL (P < 0.001), corresponding with greater gastrocnemius mass in HP than SP (+5.3%; P = 0.043).Conclusions: ER decreased absolute bulk MPS and most individual MPS rates compared with AL, and HP prolonged half-lives of most proteins across the proteome. These data suggest that HP, independent of energy intake, may reduce MPB, and reductions in MPS may contribute to lower gastrocnemius mass during ER by reducing protein deposition in obese female Zucker rats. [ABSTRACT FROM AUTHOR]

There is considerable heterogeneity in the cardiometabolic abnormalities associated with obesity. We evaluated multi-organ system metabolic function in 20 adults with metabolically healthy obesity (MHO; normal fasting glucose and triglycerides, oral glucose tolerance, intrahepatic triglyceride content, and whole-body insulin sensitivity), 20 adults with metabolically unhealthy obesity (MUO; prediabetes, hepatic steatosis, and whole-body insulin resistance), and 15 adults who were metabolically healthy lean. Compared with MUO, people with MHO had (1) altered skeletal muscle biology (decreased ceramide content and increased expression of genes involved in BCAA catabolism and mitochondrial structure/function); (2) altered adipose tissue biology (decreased expression of genes involved in inflammation and extracellular matrix remodeling and increased expression of genes involved in lipogenesis); (3) lower 24-h plasma glucose, insulin, non-esterified fatty acids, and triglycerides; (4) higher plasma adiponectin and lower plasma PAI-1 concentrations; and (5) decreased oxidative stress. These findings provide a framework of potential mechanisms responsible for MHO and the metabolic heterogeneity of obesity. This study was registered at ClinicalTrials.gov (NCT02706262). [Display omitted] • There is marked heterogeneity in metabolic abnormalities associated with obesity • Some people are resistant to adverse metabolic effects of excess adiposity • Differences involve multi-organ system function and adipose tissue/muscle biology Some people with obesity are resistant to the adverse cardiometabolic effects of excess adiposity and are considered to have "metabolically healthy obesity." Petersen et al. evaluated 100 cardiometabolic outcomes and gene expression in adipose tissue and skeletal muscle to construct a comprehensive physiological atlas of metabolically healthy and unhealthy obesity. [ABSTRACT FROM AUTHOR]

Abstract: The leaves of mulberry (Morus indica L.) of Moraceae, possess a number of bioactive compounds that fight against various ailments. In vitro free radical scavenging and in vivo antioxidant potential of mulberry leaves were investigated. Ethanolic extract of mulberry leaves was tested for antioxidant activity in vitro using butylated hydroxy toluene as a positive control. Erythrocyte membrane was used as peroxidation model system in vitro while elderly human volunteers who received mulberry leaf powder (5g/day) for 60 days served as subjects for in vivo assessment. Mulberry leaf extract scavenged DPPH, nitric oxide and superoxide radicals in a concentration dependent manner and inhibited FeSO4-induced lipid peroxidation and hydroperoxides in the erythrocyte membrane model. This was supported by significantly (p <0.01) decreased lipid peroxidation in plasma (23%) and erythrocytes (49%), significantly (p <0.01) elevated levels of non enzymatic antioxidants viz. β carotene (116%), vitamin A (69%), vitamin C (23%), vitamin E (55%) and ceruloplasmin (26%); decreased nitrite (43%) in serum and significantly elevated activity of superoxide dismutase (47%) and glutathione-S-transferase (72%) and reduced glutathione (21%, p <0.05) in erythrocytes from elderly subjects treated with mulberry leaf powder. Mulberry leaves exhibited antioxidant properties postulated to be as a result of the synergistic action of free radical scavenging compounds such as carotenoids, flavonoids, moracins and others present in the leaves. [Copyright &y& Elsevier]

Abstract: Efficacy of curry (Murraya koenigii) leaves was investigated in scavenging free radicals in vitro and controlling oxidative stress in vivo. Ethanolic extract of curry leaves (Murraya koenigii) was tested for the antioxidant activity in vitro using butylated hydroxy toluene as positive control. Erythrocyte membrane of human volunteer was used as peroxidation model system in vitro while aged human volunteers served as subjects for in vivo assessment. Curry leaf extract displayed scavenging activity against radicals viz. 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide and superoxide in a concentration dependent manner and inhibited FeSO4-induced lipid peroxides and hydroperoxides in erythrocyte membrane model. This is supported by significantly decreased lipid peroxidation in plasma and erythrocytes, significantly elevated levels of non enzymatic antioxidants (β-carotene, vitamin A, C & E) in serum and significantly decreased activity of catalase, elevated activities of superoxide dismutase and glutathione-s-transferase and raised reduced glutathione (GSH) in erythrocytes in curry leaves-treated aged subjects. In conclusion, curry leaves possess antioxidant properties and the effect is a result of synergistic action of antioxidant phytochemicals, i.e., carotenoids, flavonoids, oleoresins etc. present in the leaves. The findings of this study suggest that the leaves may be prescribed as adjunct to dietary therapy for controlling oxidative stress that causes chronic diseases in elderly. [Copyright &y& Elsevier]

Chronic glucocorticoid exposure causes insulin resistance and muscle atrophy in skeletal muscle. We previously identified phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1) as a primary target gene of skeletal muscle glucocorticoid receptors involved in the glucocorticoid-mediated suppression of insulin action. However, the in vivo functions of Pik3r1 remain unclear. Here, we generated striated muscle-specific Pik3r1 knockout (MKO) mice and treated them with a dexamethasone (DEX), a synthetic glucocorticoid. Treating wildtype (WT) mice with DEX attenuated insulin activated Akt activity in liver, epididymal white adipose tissue, and gastrocnemius (GA) muscle. This DEX effect was diminished in GA muscle of MKO mice, therefore, resulting in improved glucose and insulin tolerance in DEX-treated MKO mice. Stable isotope labeling techniques revealed that in WT mice, DEX treatment decreased protein fractional synthesis rates in GA muscle. Furthermore, histology showed that in WT mice, DEX treatment reduced GA myotube diameters. In MKO mice, myotube diameters were smaller than in WT mice, and there were more fast oxidative fibers. Importantly, DEX failed to further reduce myotube diameters. Pik3r1 knockout also decreased basal protein synthesis rate (likely caused by lower 4E-BP1 phosphorylation at Thr37/Thr46) and curbed the ability of DEX to attenuate protein synthesis rate. Finally, the ability of DEX to inhibit eIF2a phosphorylation and insulin-induced 4E-BP1 phosphorylation was reduced in MKO mice. Taken together, these results demonstrate the role of Pik3r1 in glucocorticoid-mediated effects on glucose and protein metabolism in skeletal muscle. [ABSTRACT FROM AUTHOR]