Background: Popular beliefs that breakfast is the most important meal of the day are grounded in cross-sectional observations that link breakfast to

Background: The causal nature of associations between breakfast and health remain unclear in obese individuals.Objective: We sought to conduct a rando

Context: Murine fibroblast growth factor (FGF) 21 is a nutritionally regulated hormone secreted by the liver principally in response to peroxisome proliferator-activated receptor-α (PPARα) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPARγ target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans. Objective: The aim of the study was to measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans. Design and Setting: We conducted a prospective study involving three patient groups at two university hospitals. Patients: Eight healthy male volunteers underwent a 48-h period of starvation followed by 24-h refeeding (group 1); seven obese individuals were allocated to a low-carbohydrate diet for 3 months (group 2); and three groups of healthy, overweight or obese male volunteers received treatment with a PPARα (20 μg/d GW590735) (n=6), PPARδ (10 mg/d GW501516) (n=6), or PPARγ agonist (rosiglitazone) (n=10) for 2 wk (group 3). Main Outcome Measures: Fasting plasma FGF21 and serum 3-hydroxybutyrate were measured. Results: There was no significant variation in human plasma FGF21 during fasting and refeeding. A 3-month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPARα (39%) and PPARδ (32%), but not PPARγ agonists. Conclusion: FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPARα and PPARδ and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds. FGF21 is not critical in regulating the fasting response or ketosis, but its serum level rises in response to PPARα and PPARδ agonist treatment.

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.

The aim of this study was to compare the effect of preexercise breakfast containing high- and low-glycemic index (GI) carbohydrate (CHO) (2.5g CHO/kg body mass) on muscle glycogen metabolism. On two occasions, 14 days apart, seven trained men ran at 71% maximal oxygen uptake for 30 min on a treadmill. Three hours before exercise, in a randomized order, subjects consumed either isoenergetic high- (HGI) or low-GI (LGI) CHO breakfasts that provided (per 70 kg body mass) 3.43 MJ energy, 175 g CHO, 21 g protein, and 4 g fat. The incremental areas under the 3-h plasma glucose and serum insulin response curves after the HGI meal were 3.9- (P < 0.05) and 1.4-fold greater (P < 0.001), respectively, than those after the LGI meal. During the 3-h postprandial period, muscle glycogen concentration increased by 15% (P < 0.05) after the HGI meal but remained unchanged after the LGI meal. Muscle glycogen utilization during exercise was greater in the HGI (129.1 ± 16.1 mmol/kg dry mass) compared with the LGI (87.9 ± 15.1 mmol/kg dry mass; P < 0.01) trial. Although the LGI meal contributed less CHO to muscle glycogen synthesis in the 3-h postprandial period compared with the HGI meal, a sparing of muscle glycogen utilization during subsequent exercise was observed in the LGI trial, most likely as a result of better maintained fat oxidation.