L’expression d’une CPT1 constitutivement active dans le muscle squelettique induit un remodelage musculaire mimant l’exercice et contrecarre le vieillissement musculaire
Diabetes & Metabolism Volume 37, numéro 1S1 page A19 (mars 2011)    C. Henique

Le muscle squelettique assure environ 90% de ses besoins énergétiques par la ß-oxydation mitochondriale des acides gras à chaîne longue (AGCL). L’enzyme clé de cette voie métabolique est la carnitine palmitoyltransférase 1 (CPT1) qui est inhibée par le malonyl-CoA. L’obésité, le diabète de type 2 et le vieillissement s’accompagnent d’une diminution de la capacité oxydative du muscle, d’une accumulation de lipides et d’une diminution du nombre de fibres oxydatives. De plus, la vascularisation musculaire est réduite au cours du vieillissement. Ces altérations musculaires peuvent être corrigées par l’exercice physique. Notre but a été de déterminer si une augmentation de l’oxydation musculaire des AGCL peut modifier la physiologie musculaire et contrecarrer les altérations dues au vieillissement.

Matériels et méthodes :

Nous avons exprimé une CPT1 constitutivement active (CPT1mt), i.e. insensible au malonyl-CoA, dans le tibialis anterior (TA) de souris âgées de 2 et 20 mois par la technique d’électroporation in vivo. Après 30 jours, nous avons évalué les conséquences de cette expression sur la composition en fibres musculaires, la vascularisation et la résistance à la fatigue.

Résultats :

Chez les souris jeunes (2 mois), l’expression de la CPT1mt dans le TA entraîne une augmentation significative du poids du TA (+36%), accompagnée d’un changement de la composition en type de fibres musculaires (+25% de fibres oxydatives) et d’une augmentation du nombre de capillaires (+24%). Ces modifications sont associées à une augmentation du contenu musculaire en glucose-6-phosphate (+19%) et en glycogène (+41%). De plus, l’expression de la CPT1mt diminue la fatigabilité musculaire (− 20%). Chez les souris âgées (20 mois), l’expression de la CPT1mt réduit la perte de masse musculaire et contrecarre la diminution de la vascularisation.

Conclusion :

De façon similaire à l’exercice physique, la CPT1 module la plasticité musculaire et l’angiogenèse. De plus, nos résultats suggèrent que cibler la CPT1 permet de contrecarrer certaines altérations musculaires observées au cours du vieillissement.

Commenter    |     0 commentaire

Communication entre le muscle squelettique insulino-résistant et les cellules bêta pancréatiques
Diabetes & Metabolism Volume 37, numéro 1S1 page A6 (mars 2011)    K. Bouzakri

Le diabète de type 2 est caractérisé par une insulino-résistance et une diminution de la sécrétion d’insuline. Nous avons exploré la communication potentielle entre le muscle squelettique humain insulino-résistant et les cellules beta-pancréatiques primaire.

Matériels et méthodes :

Les cellules musculaire squelettiques humaines ont été cultivées avec du TNF-alpha pour induire une résistance à l’insuline. L’expression d’ARNm pour des cytokines a été analysée et comparée avec les contrôles (sans TNF-alpha). Les milieux conditionnés ont été collecté et les cytokines ont été mesurées par membranes à anticorps. Des cellules beta-pancréatiques primaire humaine et de rat ont été utilisés pour explorer l’impact des milieux conditionnés sur l’apoptose, la prolifération, la sécrétion d’insuline à court terme ainsi que la phosphorylation et l’expression de protéines clefs.

Résultats :

Les myotubes humains expriment et secrètent différentes myokines, selon leur sensibilité à l’insuline, qui exercent des effets différentiels sur les cellules bêta-pancréatiques. Le milieu conditionné des myotubes contrôle (CM) augment la prolifération et la sécrétion d’insuline stimulée par glucose dans les cellules bêta-pancréatiques primaire, tandis que le milieu conditionné au TNF-alpha des myotubes résistant à l’insuline (TM) exerce des effets nuisibles qui sont indépendants du TNF-alpha, (augmentation de l’apoptose et diminution de la prolifération) ou dépendant du TNF-alpha (secretion de l’insuline). La diminution de MAP4K4 dans les cellules bêta prévient ces effets. GLP-1 protège les cellules bêta contre la diminution de prolifération et l’apoptose induite par TM, tandis qu’IL-1RA protège uniquement contre l’apoptose.

Conclusion :

Nos données suggèrent une nouvelle route possible dans la communication entre le muscle squelettique et les cellules bêta-pancréatiques qui est modulée par la résistance à l’insuline. Celle-ci pourraient contribuer à la masse fonctionnelle cellulaire normale des cellules bêta-pancréatiques chez des sujets sains, ainsi que la diminution de cette dernière observée dans le diabète de type 2.

Commenter    |     0 commentaire

Interaction between Testosterone and Growth Hormone on Whole-Body Protein Anabolism Occurs in the Liver
The Journal of Clinical Endocrinology & Metabolism   2011 Vol. 96 (4): 1060-1067     Vita Birzniece

Context:

GH and testosterone both exert protein-anabolic effects and may act synergistically. Liver and muscle are major sites of protein metabolism.

Objective:

Our objective was to determine whether the site of GH and testosterone interaction on protein metabolism is primarily hepatic or extrahepatic.

Design:

In this open-label randomized crossover study, the impact on whole-body protein metabolism of oral (solely hepatic testosterone exposure) and transdermal (systemic testosterone exposure) testosterone replacement in the presence or absence of GH was compared.

Patients and Intervention:

Eleven hypopituitary men with GH and testosterone deficiency were randomized to 2-wk treatments with transdermal testosterone (10 mg) or oral testosterone (40 mg), with or without GH replacement (0.6 mg/d). The dose of testosterone administered orally achieves physiological portal testosterone concentrations without spillover into the systemic circulation.

Main Outcome Measures:

Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown, and leucine oxidation (Lox), a measure of irreversible protein loss, were estimated at the end of each treatment.

Results:

In the absence of GH, neither transdermal nor oral testosterone affected LRa or Lox. GH therapy significantly increased LRa, an effect equally reduced by transdermal and oral testosterone administration. GH replacement alone did not significantly change Lox, whereas addition of testosterone treatment reduced Lox, with the effect not significantly different between transdermal and oral testosterone.

Conclusions:

In the doses used, testosterone stimulates protein anabolism by reducing protein breakdown and oxidation only in the presence of GH. Because the net effect on protein metabolism during GH therapy is not different between systemic and solely hepatic testosterone administration, we conclude that the liver is the primary site of this hormonal interaction.

Commenter    |     0 commentaire

Caffeinated Coffee Does Not Acutely Affect Energy Intake, Appetite, or Inflammation but Prevents Serum Cortisol Concentrations from Falling in Healthy Men
Anna Gavrieli         J. Nutr. April 1, 2011 vol. 141 no. 4 703-707

Our aim in this crossover study was to investigate the acute effects of caffeinated and decaffeinated coffee consumption on appetite feelings, energy intake, and appetite-, inflammation-, stress-, and glucose metabolism-related markers. Sixteen healthy men (age range, 21–39 y; BMI range, 19.7–28.6 kg/m2) received in a random order on 3 separate occasions a standard breakfast snack with 200 mL of either caffeinated coffee (3 mg caffeine/kg body weight), decaffeinated coffee, or water (control). Before intervention (−15 min) and at standard time points following breakfast consumption (0, 15, 30, 60, 90, 120, 150, and 180 min), participants recorded their appetite feelings and we collected blood samples for measurements of circulating glucose, insulin, cortisol, and appetite- and inflammation-related markers. At 180 min, participants consumed a meal ad libitum. The appetite-related ratings, the appetite plasma hormonal responses as well as the plasma glucose, serum insulin, and plasma and serum inflammatory marker responses did not show an overall intervention effect or a time x intervention interaction. Ad libitum energy intake did not differ among the 3 interventions. However, a significant intervention effect (P = 0.04) and a time x intervention interaction (P-interaction = 0.02) were found for serum cortisol; cortisol concentrations were significantly higher following the caffeinated coffee intervention, compared to control, at 60 min and thereafter. In conclusion, the usually consumed amount of caffeinated coffee does not have short-term effects on appetite, energy intake, glucose metabolism, and inflammatory markers, but it increases circulating cortisol concentrations in healthy men.

Commenter    |     0 commentaire

Potassium Intake, Stroke, and Cardiovascular Disease A Meta-Analysis of Prospective Studies
J Am Coll Cardiol, 2011; 57:1210-1219           Lanfranco D’Elia

Objectives:

The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD).

Background:

Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent.

Methods:

We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed.

Results:

Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037).

Conclusions:

Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases.

Commenter    |     0 commentaire

Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans
The Journal of Clinical Endocrinology & Metabolism, Vol. 96 (3): 463-472 2011 Joshua J. Gooley

Context:

Millions of individuals habitually expose themselves to room light in the hours before bedtime, yet the effects of this behavior on melatonin signaling are not well recognized.

Objective:

We tested the hypothesis that exposure to room light in the late evening suppresses the onset of melatonin synthesis and shortens the duration of melatonin production.

Design:

In a retrospective analysis, we compared daily melatonin profiles in individuals living in room light (<200 lux) vs. dim light (<3 lux).

Healthy volunteers (n = 116, 18–30 yr) were recruited from the general population to participate in one of two studies.

Participants lived in a General Clinical Research Center for at least five consecutive days.

Individuals were exposed to room light or dim light in the 8 h preceding bedtime.

Melatonin duration, onset and offset, suppression, and phase angle of entrainment were determined.

Compared with dim light, exposure to room light before bedtime suppressed melatonin, resulting in a later melatonin onset in 99.0% of individuals and shortening melatonin duration by about 90 min. Also, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50% in most (85%) trials.

These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body’s internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.

Commenter    |     0 commentaire

Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults
Todd A. Trappe AJP - Regu Physiol March 2011 vol. 300 no. 3 R655-R662

Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 ± 2 yr; n = 12), acetaminophen (64 ± 1 yr; n = 11; 4 g/day), and ibuprofen (64 ± 1 yr; n = 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar (P > 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 ± 14 cm3, 12.5%; ibuprofen: 84 ± 10 cm3, 10.9%) and muscle strength (acetaminophen: 19 ± 2 kg; ibuprofen: 19 ± 2 kg) to a greater extent (P

< 0.05) than placebo (muscle volume: 69 ± 12 cm3, 8.6%; muscle strength: 15 ± 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced (P >

0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced (P > 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 ± 8%; P

< 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles (P >

0.05). Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.

Commenter    |     3 commentaires