We determined the effects of intravenous infusion of amino acids (AA) at serum insulin of 5, 30, 72, and 167 mU/l on anabolic signaling, expression of ubiquitin-proteasome components, and protein turnover in muscles of healthy young men. Tripling AA availability at 5 mU/l insulin doubled incorporation of [1-¹³C]leucine [i.e., muscle protein synthesis (MPS), P < 0.01] without affecting the rate of leg protein breakdown (LPB; appearance of d₅-phenylalanine). While keeping AA availability constant, increasing insulin to 30 mU/l halved LPB ( P < 0.05) without further inhibition at higher doses, whereas rates of MPS were identical to that at 5 mU/l insulin. The phosphorylation of PKB Ser⁴⁷³ and p70^S6k Thr³⁸⁹ increased concomitantly with insulin, but whereas raising insulin to 30 mU/l increased the phosphorylation of mTOR Ser²⁴⁴⁸, 4E-BP1 Thr^37/46, or GSK3β Ser⁹ and decreased that of eEF2 Thr⁵⁶, higher insulin doses to 72 and 167 mU/l did not augment these latter responses. MAFbx and proteasome C2 subunit proteins declined as insulin increased, with MuRF-1 expression largely unchanged. Thus increasing AA and insulin availability causes changes in anabolic signaling and amounts of enzymes of the ubiquitin-proteasome pathway, which cannot be easily reconciled with observed effects on MPS or LPB.

Chrono-nutrition is an emerging research field in nutritional epidemiology that encompasses 3 dimensions of eating behavior: timing, frequency, and regularity. To date, few studies have investigated how an individual's circadian typology, i.e., one's chronotype, affects the association between chrono-nutrition and cardiometabolic health. This review sets the directions for future research by providing a narrative overview of recent epidemiologic research on chronotype, its determinants, and its association with dietary intake and cardiometabolic health. Limited research was found on the association between chronotype and dietary intake in infants, children, and older adults. Moreover, most of the evidence in adolescents and adults was restricted to cross-sectional surveys with few longitudinal cohorts simultaneously collecting data on chronotype and dietary intake. There was a gap in the research concerning the association between chronotype and the 3 dimensions of chrono-nutrition. Whether chronotype modifies the association between diet and cardiometabolic health outcomes remains to be elucidated. In conclusion, further research is required to understand the interplay between chronotype, chrono-nutrition, and cardiometabolic health outcomes.

The importance of the circadian rhythm in regulating human food intake behaviour and metabolism has long been recognised. However, little is known as to how energy intake is distributed over the day in existing populations, and its potential association with obesity. The present review describes global trends in time-of-day of energy intake in the general population based on data from cross-sectional surveys and longitudinal cohorts. Evidence of the association between time-of-day of energy intake and obesity is also summarised. Overall, there were a limited number of cross-sectional surveys and longitudinal cohorts that provided data on time-of-day of energy intake. In the identified studies, a wide variation in time-of-day of energy intake was observed, with patterns of energy distribution varying greatly by country and geographical area. In relation to obesity, eight cross-sectional surveys and two longitudinal cohorts were identified. The association between time-of-day of energy intake and obesity varied widely, with several studies reporting a positive link between evening energy intake and obesity. In conclusion, the current review summarises global trends in time-of-day of energy intake. The large variations across countries and global regions could have important implications to health, emphasising the need to understand the socio-environmental factors guiding such differences in eating patterns. Evidence of the association between time-of-day of energy intake and BMI also varied. Further larger scale collaborations between various countries and regions are needed to sum data from existing surveys and cohorts, and guide our understanding of the role of chrono-nutrition in health.

Background: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations.

Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.

Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (−1.91 ± 0.99 kilograms) almost entirely due to fat loss (−1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (−1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (−0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (−0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (−0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups (P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health.