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Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (-12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+ 17%) with hyperleptinemia and hyper-insulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood. leptin resistance; hypothalamus; high-fat diet

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CR[F.sub.2] receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CR[F.sub.1] receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may he associated with changes in basal CRF and UCN I mRNA expression. rats; food intake; corticosterone; corticotropin-releasing factor mRNA; urocortin I mRNA

Five days of a high-fat diet while training, followed by 1 day of carbohydrate (CHO) restoration, increases rates of whole body fat oxidation and decreases CHO oxidation during aerobic cycling. The mechanisms responsible for these shifts in fuel oxidation are unknown but involve up- and downregulation of key regulatory enzymes in the pathways of skeletal muscle fat and CHO metabolism, respectively. This study measured muscle PDH and HSL activities before and after 20 min of cycling at 70% V[O.sub.2 peak] and 1 min of sprinting at 150% peak power output (PPO). Estimations of muscle glycogenolysis were made during the initial minute of exercise at 70% V[O.sub.2 peak] and during the 1-min sprint. Seven male cyclists undertook this exercise protocol on two occasions. For 5 days, subjects consumed in random order either a high-CHO (HCHO) diet (10.3 g*[kg.sup.-1]*[day.sup.-1] CHO, or ~70% of total energy intake) or an isoenergetic high-fat (FAT-adapt) diet (4.6 g*[kg.sup.-]*[day.sup.-1] FAT, or 67% of total energy) while undertaking supervised aerobic endurance training. On day 6 for both treatments, subjects ingested an HCHO diet and rested before their experimental trials on day 7. This CHO restoration resulted in similar resting glycogen contents (FAT-adapt 873 [+ or -] 121 vs. HCHO 868 [+ or -] 120 [micro]mol glucosyl units/g dry wt). However, the respiratory exchange ratio was lower during cycling at 70% V[O.sub.2 peak] in the FAT-adapt trial, which resulted in an ~45% increase and an ~30% decrease in fat and CHO oxidation, respectively. PDH activity was lower at rest and throughout exercise at 70% V[O.sub.2 peak] (1.69 [+ or -] 0.25 vs. 2.39 [+ or -] 0.19 mmol*kg wet [wt.sup.-1]*[min.sup.-1]) and the 1-min sprint in the FAT-adapt vs. the HCHO trial. Estimates of glycogenolysis during the 1st min of exercise at 70% V[O.sub.2 peak] and the 1-min sprint were also lower after FAT-adapt (9.1 [+ or -] 1.1 vs. 13.4 [+ or -] 2.1 and 37.3 [+ or -] 5.1 vs. 50.5 [+ or -] 2.7 glucosyl units*kg dry [wt.sup.-l]*[min.sup.-1]). HSL activity was ~20% higher (P = 0.12) during exercise at 70% V[O.sub.2 peak] after FAT-adapt. Results indicate that previously reported decreases in whole body CHO oxidation and increases in fat oxidation after the FAT-adapt protocol are a function of metabolic changes within skeletal muscle. The metabolic signals responsible for the shift in muscle substrate use during cycling at 70% V[O.sub.2 peak] remain unclear, but lower accumulation of free ADP and AMP after the FAT-adapt trial may be responsible for the decreased glycogenolysis and PDH activation during sprinting. skeletal muscle metabolism; pyruvate dehydrogenase; substrate phosphorylation; fat oxidation; carbohydrate oxidation