Maternal exercise modifies body composition and energy substrates handling in male offspring fed a high-fat/high-sucrose diet.

KEY POINTS: Maternal training during gestation enhances offspring body composition and energy substrates handling in early adulthood. Offspring nutrition also plays a role as some beneficial effects of maternal training during gestation disappear after consumption of a high-fat diet. ABSTRACT: Maternal exercise during gestation has been reported to modify offspring metabolism and health. Whether these effects are exacerbated when offspring are receiving a high-fat diet remains unclear. Our purpose was to evaluate the effect of maternal exercise before and during gestation on the offspring fed a high-fat/high-sucrose diet (HF) by assessing its body composition, pancreatic function and energy substrates handling by two major glucose-utilizing tissues: liver and muscle. Fifteen-week-old nulliparous female Wistar rats exercised 4 weeks before as well as during gestation at a constant submaximal intensity (TR) or remained sedentary (CT). At weaning, pups from each group were fed either a standard diet (TRCD or CTCD) or a high-fat/high-sucrose diet (TRHF or CTHF) for 10 weeks. Offspring from TR dams gained less weight compared to those from CT dams. Selected fat depots were larger with the HF diet compared to control diet (CD) but significantly smaller in TRHF compared to CTHF. Surprisingly, the insulin secretion index was higher in islets from HF offspring compared to CD. TR offspring showed a higher muscle insulin sensitivity estimated by the ratio of phosphorylated protein kinase B to total protein kinase B compared with CT offspring (+48%, P < 0.05). With CD, permeabilized isolated muscle fibres from TR rats displayed a lower apparent affinity constant (Km ) for pyruvate and palmitoyl coenzyme A as substrates compared to the CT group (-46% and -58%, respectively, P < 0.05). These results suggest that maternal exercise has positive effects on young adult offspring body composition and on muscle carbohydrate and lipid metabolism depending on the nutritional status.

Short-term and long-term effects of submaximal maternal exercise on offspring glucose homeostasis and pancreatic function.

Only a few studies have explored the effects of maternal exercise during gestation on adult offspring metabolism. We set out to test whether maternal controlled submaximal exercise maintained troughout all gestational periods induces persistant metabolic changes in the offspring. We used a model of 15-wk-old nulliparous female Wistar rats that exercised (trained group) before and during gestation at a submaximal intensity or remained sedentary (control group). At weaning, male offspring from trained dams showed reduced basal glycemia (119.7 ± 2.4 vs. 130.5 ± 4.1 mg/dl, P < 0.05), pancreas relative weight (3.96 ± 0.18 vs. 4.54 ± 0.14 g/kg body wt, P < 0.05), and islet mean area (22,822 ± 4,036 vs. 44,669 ± 6,761 µm(2), P < 0.05) compared with pups from control dams. Additionally, they had better insulin secretory capacity when stimulated by 2.8 mM glucose + 20 mM arginine compared with offspring from control dams (+96%, P < 0.05). At 7 mo of age, offspring from trained mothers displayed altered glucose tolerance (AUC = 15,285 ± 527 vs. 11,898 ± 988 mg·dl(-1)·120 min, P < 0.05) and decreased muscle insulin sensitivity estimated by the phosphorylated PKB/total PKB ratio (-32%, P < 0.05) and tended to have a reduced islet insulin secretory capacity compared with rats from control dams. These results suggest that submaximal maternal exercise modifies short-term male offspring pancreatic function and appears to have rather negative long-term consequences on sedentary adult offspring glucose handling.

Muscle Oxygen Supply and Use in Type 1 Diabetes, From Ambient Air to the Mitochondrial Respiratory Chain: Is There a Limiting Step?

OBJECTIVE: Long before clinical complications of type 1 diabetes (T1D) develop, oxygen supply and use can be altered during activities of daily life. We examined in patients with uncomplicated T1D all steps of the oxygen pathway, from the lungs to the mitochondria, using an integrative ex vivo (muscle biopsies) and in vivo (during exercise) approach. RESEARCH DESIGN AND METHODS: We compared 16 adults with T1D with 16 strictly matched healthy control subjects. We assessed lung diffusion capacity for carbon monoxide and nitric oxide, exercise-induced changes in arterial O2 content (SaO2, PaO2, hemoglobin), muscle blood volume, and O2 extraction (via near-infrared spectroscopy). We analyzed blood samples for metabolic and hormonal vasoactive moieties and factors that are able to shift the O2-hemoglobin dissociation curve. Mitochondrial oxidative capacities were assessed in permeabilized vastus lateralis muscle fibers. RESULTS: Lung diffusion capacity and arterial O2 transport were normal in patients with T1D. However, those patients displayed blunted exercise-induced increases in muscle blood volume, despite higher serum insulin, and in O2 extraction, despite higher erythrocyte 2,3-diphosphoglycerate. Although complex I- and complex II-supported mitochondrial respirations were unaltered, complex IV capacity (relative to complex I capacity) was impaired in patients with T1D, and this was even more apparent in those with long-standing diabetes and high HbA1c. [Formula: see text]O2max was lower in patients with T1D than in the control subjects. CONCLUSIONS: Early defects in microvascular delivery of blood to skeletal muscle and in complex IV capacity in the mitochondrial respiratory chain may negatively impact aerobic fitness. These findings are clinically relevant considering the main role of skeletal muscle oxidation in whole-body glucose disposal.

Effect of training on beta1 beta2 beta3 adrenergic and M2 muscarinic receptors in rat heart.

OBJECTIVE: Physical training is known to alter several cardiovascular parameters. These adaptations are for a great part linked to an alteration of the myocardial responses to its autonomic nervous regulation. To further explain the parasympathetic and catecholamine effects, we hypothesized that endurance training could modify rat myocardial beta1, beta2, beta3 adrenoreceptors (AR) and M2 muscarinic cholinergic receptor (AchR) densities. METHODS: Two groups of adults female Wistar rats were studied: controls (C) (N = 7) and trained (T) (N = 9). An 8-wk treadmill training protocol was performed, 5 d x wk and of 1 h x d. At the end of the training session, left ventricle and atria muscle were isolated and weighed. Then, quantification of beta1, beta2, beta3 AR and M2 AchR was performed using Western blot analysis. RESULTS: M2 AchR densities were not modified in left ventricle or in atria by training (respectively, 100 +/- 22%, C vs 101 +/- 14%, T and 100 +/- 23%, C vs 119 +/- 30%, T). Concerning the left ventricle beta AR isoforms, beta1AR density was decreased in T (80 +/- 10% T vs 100 +/- 14% C, P = 0.01), beta2AR was unaltered (102 +/- 12%, T vs 100 +/- 17%, C), and beta3 AR density was increased in T (139 +/- 38% T vs 100 +/- 15% C; P < 0.05). CONCLUSIONS: Our results show for the first time that in female rats an 8-wk treadmill training protocol alters specifically the left ventricle beta AR isoforms densities but not the M2 AchR one. These results could explain some of the beneficial cardiovascular adaptations of the physically trained heart.

Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in response to formoterol administration in rat skeletal muscle.

Administration of ß2-agonists triggers skeletal muscle anabolism and hypertrophy. We investigated the time course of the molecular events responsible for rat skeletal muscle hypertrophy in response to 1, 3 and 10 days of formoterol administration (i.p. 2000µg/kg/day). A marked hypertrophy of rat tibialis anterior muscle culminated at day 10. Phosphorylation of Akt, ribosomal protein S6, 4E-BP1 and ERK1/2 was increased at day 3, but returned to control level at day 10. This could lead to a transient increase in protein translation and could explain previous studies that reported increase in protein synthesis following ß2-agonist administration. Formoterol administration was also associated with a significant reduction in MAFbx/atrogin-1 mRNA level (day 3), suggesting that formoterol can also affect protein degradation of MAFbx/atrogin1 targeted substrates, including MyoD and eukaryotic initiation factor-3f (eIF3-f). Surprisingly, mRNA level of autophagy-related genes, light chain 3 beta (LC3b) and gamma-aminobutyric acid receptor-associated protein-like 1 (Gabarapl1), as well as lysosomal hydrolases, cathepsin B and cathepsin L, was significantly and transiently increased after 1 and/or 3 days, suggesting that autophagosome formation would be increased in response to formoterol administration. However, this has to be relativized since the mRNA level of Unc-51-like kinase1 (Ulk1), BCL2/adenovirus E1B interacting protein3 (Bnip3), and transcription factor EB (TFEB), as well as the protein content of Ulk1, Atg13, Atg5-Atg12 complex and p62/Sqstm1 remained unchanged or was even decreased in response to formoterol administration. These results demonstrate that the effects of formoterol are mediated, in part, through the activation of Akt-mTOR pathway and that other signaling pathways become more important in the regulation of skeletal muscle mass with chronic administration of ß2-agonists.

Exercise training and cardiovascular risk factors in type 1 diabetic adolescent girls.

Sixteen postmenarcheal Type 1 diabetic adolescent girls were randomized into training (involving aerobic and strength exercises) and nontraining groups. Body composition (skinfold thickness), aerobic fitness (PWC170), plasma lipids, serum apolipoproteins, lipoprotein(a), leptin, and adiponectin were assessed before and after the 6-month period. After the 6-month period, fat mass and leptin increased significantly in the nontraining group but not in the training group. Conversely, in the latter group, fat-free mass increased (P < .01). Moreover, PWC170 improved and apolipoproteinB:apolipoproteinA-1 ratio decreased with physical training (P < .05). Thus, physical training reduces cardiovascular risks and the increase of insulin resistance risk factors in diabetic adolescent girls.

Plasma glucose, insulin and catecholamine responses to a Wingate test in physically active women and men.

The influence of gender on the glucose response to exercise remains contradictory. Moreover, to our knowledge, the glucoregulatory responses to anaerobic sprint exercise have only been studied in male subjects. Hence, the aim of the present study was to compare glucoregulatory metabolic (glucose and lactate) and hormonal (insulin, catecholamines and estradiol only in women) responses to a 30-s Wingate test, in physically active students. Eight women [19.8 (0.7) years] and eight men [22.0 (0.6) years] participated in a 30-s Wingate test on a bicycle ergometer. Plasma glucose, insulin, and catecholamine concentrations were determined at rest, at the end of both the warm-up and the exercise period and during the recovery (5, 10, 20, and 30 min). Results showed that the plasma glucose increase in response to a 30-s Wingate test was significantly higher in women than in men [0.99 (0.15) versus 0.33 (0.20) mmol l(-1) respectively, P<0.05]. Plasma insulin concentrations peaked at 10 min post-exercise and the increase between this time of recovery and the end of the warm-up was also significantly higher in women than in men [14.7 (2.9) versus 2.3 (1.9) pmol l(-1) respectively, P<0.05]. However, there was no gender difference concerning the catecholamine response. The study indicates a gender-related difference in post-exercise plasma glucose and insulin responses after a supramaximal exercise.

[Catecholamine response to the Wingate test in untrained women]. / Réponse en catécholamines à l'épreuve de Wingate chez la femme non-entraînée.

Supramaximal exercises are well known to induce a severe stress on the adrenal medulla and nervous sympathetic system. This stress induces increased plasma catecholamines concentrations. The responses of catecholamines to supramaximal exercises in women are still not well characterized and have been studied mostly in trained subjects. Hence the aim of the present study was to evaluate plasma catecholamine responses to a Wingate test in young and untrained women (n = 6) and men (n = 7). Venous plasma catecholamine concentrations were determined by HPLC, at rest, at the end of the warm-up and of the exercise, and during recovery (5, 10, 20, and 30 mn). Our results failed to show any significant difference in resting catecholamine concentrations ([A]p: 0.41 +/- 0.05 vs. 0.45 +/- 0.05 nmol. L-1; [NA]p: 3.28 +/- 0.68 vs. 2.58 +/- 0.26 nmol.L-1), kinetics, and maximal plasma catecholamine concentrations (Amax: 4.47 +/- 1.08 vs. 3.31 +/- 0.63 nmol.L-1; NAmax: 18.05 +/- 1.11 vs. 14.01 +/- 2.02 nmol.L-1) in response to the Wingate test between women and men, respectively. The Amax/NAmax ratio used as an index of adrenal medulla sensitivity to sympathetic input was also similar between genders. In conclusion, this study was able to demonstrate, in untrained subjects, that gender did not alder the sympatho-adrenergic response induced by a severe stress.