Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle

Glycogen stored in skeletal muscle is the main fuel for endurance exercise. The present study examined the effects of oral hydroxycitrate (HCA) supplementation on post-meal glycogen synthesis in exercised human skeletal muscle. Eight healthy male volunteers (aged 22·0 (se 0·3) years) completed a 60-min cycling exercise at 70–75 % \dot {>V}O_{2\hairsp max} and received HCA or placebo in a crossover design repeated after a 7 d washout period. They consumed 500 mg HCA or placebo with a high-carbohydrate meal (2 g carbohydrate/kg body weight, 80 % carbohydrate, 8 % fat, 12 % protein) for a 3-h post-exercise recovery. Muscle biopsy samples were obtained from vastus lateralis immediately and 3 h after the exercise. We found that HCA supplementation significantly lowered post-meal insulin response with similar glucose level compared to placebo. The rate of glycogen synthesis with the HCA meal was approximately onefold higher than that with the placebo meal. In contrast, GLUT4 protein level after HCA supplementation was significantly decreased below the placebo level, whereas expression of fatty acid translocase (FAT)/CD36 mRNA was significantly increased above the placebo level. Furthermore, HCA supplementation significantly increased energy reliance on fat oxidation, estimated by the gaseous exchange method. However, no differences were found in circulating NEFA and glycerol levels with the HCA meal compared with the placebo meal. The present study reports the first evidence that HCA supplementation enhanced glycogen synthesis rate in exercised human skeletal muscle and improved post-meal insulin sensitivity.

Relationship between changes in body composition and insulin responsiveness in models of the aging rat

Increased body weight (BW) is one of several confounding factors that may contribute to the development of insulin resistance in human aging. Therefore aging-associated increase in BW was determined by 3H2O in Sprague-Dawley (S-D, n = 40) rats and was highly correlated with increased lean body mass (LBM), fat mass (FM), and plasma insulin and free fatty acid (FFA) levels (r2 > 0.850, P < 0.01 for all). Insulin (18 mU.kg-1.min-1) responsiveness (Rd; 270 +/- 10 mumol.kg LBM-1.min-1, P < 0.01) decreased by 17% between 2 and 4 mo but did not decline further at 14 mo. This decrease was inversely correlated with the increase in FM between 2 and 4 mo (r2 = 0.522, P < 0.05). The decline in Rd was accompanied by an approximately 20% decrease in glycolytic rate by 4 mo (P < 0.01) and in glycogen synthesis rate at 14 mo (P < 0.01) compared with 2-mo rats. Thus early impairment in intracellular glucose metabolism occurred concomitantly with an initial, rapid, and disproportionate increase in FM compared with LBM. Further increases in FM after 4 mo of age were not associated with a further decrease in insulin responsiveness in either S-D or Fischer 344 aging rats.

In vivo regulation of rat muscle glycogen resynthesis after intense exercise

Time courses of the glycogen synthesis rate and of the glucose 6-phosphate (G-6-P) concentration after an electrically induced exercise were followed in the anesthetized rat gastrocnemius by in vivo 13C and 31P nuclear magnetic resonance (NMR) spectroscopy, respectively. The ratio of glycogen synthase I to glycogen synthase I and D (I/I+D) and allosteric activation by G-6-P were also studied in vitro on muscles sampled at rest and 10 min (early recovery) and 100 min (late recovery) after exercise. From early recovery to late recovery, the in vivo glycogen synthesis rate dropped from 0.46 +/- 0.06 to 0.11 +/- 0.04 mmol.kg wet tissue-1.min-1, the G-6-P concentration from 0.83 +/- 0.08 to 0.32 +/- 0.05 mmol/kg wet tissue, and I/I+D from 83 +/- 4 to 47 +/- 1%. The combination of the changes in G-6-P concentration and in I/I+D quantitatively describes the fourfold decrease in glycogen synthesis rate from early to late recovery. These results demonstrate that phosphorylation, determining glycogen synthase I/I+D, and allosteric control of glycogen synthase by G-6-P contribute approximately equally to the regulation of the postexercise in vivo glycogen synthesis rate.