1 Département Obésité et Métabolisme, Institut National de la Santé et de la Recherche Médicale, Unité 858, Institut de Médecine Moléculaire de Rangueil; 2 Faculté de Médecine de Toulouse Service de ...Pharmacologie, Centre Hospitalier Universitaire; 3 Hôpitaux Purpan et Larrey, Toulouse, France; 4 Institut National de la Santé et de la Recherche Médicale, Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; and 5 Centre d'Investigation Clinique, Hôpital Pur pan, Toulouse, France
Submitted 12 February 2008
; accepted in final form 10 June 2008
Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol a β-adrenergic receptor (AR) antagonist. Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine ( -AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the 2 -antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise no matter which was used probe in both groups. Compared with the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the β-AR blocker. Tertatolol reduced plasma nonesterified fatty acids and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma nonesterified fatty acids, glycerol, and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased 2 -antilipolytic effect, the lipid mobilization in subcutaneous adipose tissue that persists during exercise under β-blockade is not dependent on catecholamine action. On the basis of correlation findings, it seems to be related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.
microdialysis; tertatolol; atrial natriuretic peptide; insulin
Address for reprint requests and other correspondence: M. Berlan, INSERM U858-I2MR, Institut de Médecine Moléculaire de Rangueil 1, Ave. Jean Poulhès, BP 84225, F 31432 Toulouse Cedex 4, France (e-mail: berlan{at}cict.fr )
The number of older obese adults is increasing worldwide. Whether obese adults show similar health benefits in response to lifestyle interventions at different ages is unknown. The study enrolled 25 ...obese men (BMI 31-39 kg/m2) in two arms according to age (30-40 and 60-70 years old). Participants underwent an 8-week intervention with moderate calorie restriction (~20% below individual energy requirements) and supervised endurance training resulting in ~5% weight loss. Body composition was measured using dual energy X-Ray absorptiometry. Insulin sensitivity was assessed during a hypersinsulinemic euglycemic clamp. Cardiometabolic profile was derived from blood parameters. Subcutaneous fat and vastus lateralis muscle biopsies were used for ex vivo analyses. Two-way repeated-measure ANOVA and linear mixed models were used to evaluate the response to lifestyle intervention and comparison between the two groups. Fat mass was decreased and bone mass was preserved in the two groups after intervention. Muscle mass decreased significantly in older obese men. Cardiovascular risk (Framingham risk score, plasma triglyceride and cholesterol) and insulin sensitivity were greatly improved to a similar extent in the two age groups after intervention. Changes in adipose tissue and skeletal muscle transcriptomes were marginal. Analysis of the differential response to the lifestyle intervention showed tenuous differences between age groups. These data suggest that lifestyle intervention combining calorie restriction and exercise shows similar beneficial effects on cardiometabolic risk and insulin sensitivity in younger and older obese men. However, attention must be paid to potential loss of muscle mass in response to weight loss in older obese men.
Objective: To explore sex differences in the regulation of lipolysis during exercise, the lipid‐mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were ...studied using microdialysis.
Research Methods and Procedures: Subjects matched for age, BMI, and physical fitness performed two 30‐minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (Vo2max) and the second test at 30% and 70% of their Vo2max.
Results: In both groups, an exercise‐dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine α‐adrenergic receptor (AR) antagonist added to a dialysis probe potentiated exercise‐induced lipolysis only in men. In a probe containing phentolamine plus propranolol (β‐AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% Vo2max. A significant reduction of EGC (when compared with the control probe) was observed in women at 70% Vo2max. At each exercise power, the plasma non‐esterified fatty acid and glycerol concentrations were higher in women. Exercise‐induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups.
Discussion: Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. α2‐Anti‐lipolytic effect was functional in SCAT of men only. The major finding is that during low‐to‐moderate exercise periods (30% and 50% Vo2max), lipid mobilization in SCAT relies less on catecholamine‐dependent stimulation of β‐ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.
1 Institut National de la Santé et de la Recherche Médicale, U858, Laboratoire de Recherche sur les Obésités, Institut de Médecine Moléculaire de Rangueil, 2 Université Paul Sabatier, Institut Louis ...Bugnard, IFR31, 3 Faculté de Médecine, Laboratoire de Pharmacologie Clinique et Médicale, and 4 Centre d'Investigation Clinique, Toulouse, France
Submitted 6 March 2007
; accepted in final form 29 May 2007
Head-down bed rest (HDBR) increases plasma levels of atrial natriuretic peptide (ANP) and decreases norepinephrine levels. We previously demonstrated that ANP promotes lipid mobilization and utilization, an effect independent of sympathetic nervous system activation, when infused into lean healthy men at pharmacological doses. The purpose of the present study was to demonstrate that a physiological increase in ANP contributes to lipid mobilization and oxidation in healthy young men. Eight men were positioned for 4 h in a sitting (control) or in a HDBR position. Indexes of lipid mobilization and hormonal changes were measured in plasma. Extracellular glycerol, an index of lipolysis, was determined in subcutaneous adipose tissue (SCAT) with a microdialysis technique. A twofold increase in plasma ANP concentration was observed after 60 min of HDBR, and a plateau was maintained thereafter. Plasma norepinephrine decreased by 30–40% during HDBR, while plasma insulin and glucose levels did not change. The level of plasma nonesterified fatty acids was higher during HDBR. SCAT lipolysis, as reflected by interstitial glycerol, as well as interstitial cGMP, the second messenger of the ANP pathway, increased during HDBR. This was associated with an increase in blood flow observed throughout HDBR. Significant changes in respiratory exchange ratio and percent use of lipid and carbohydrate were seen only after 3 h of HDBR. Thus the proportion of lipid oxidized increased by 40% after 3 h of HDBR. The rise in plasma ANP during HDBR was associated with increased lipolysis in SCAT and whole body lipid oxidation. In this physiological setting, independent of increasing catecholamines, our study suggests that ANP contributes to lipid mobilization and oxidation in healthy young men.
lipolysis; lipid oxidation
Address for reprint requests and other correspondence: M. Lafontan, Inserm U858-I2MR-Equipe 1, 1 Ave. Jean Poulhès BP 84225, 31432 Toulouse Cedex 4, France (e-mail: max.lafontan{at}toulouse.inserm.fr )
OBJECTIVE: To explore sex differences in the regulation of lipolysis during exercise, the lipid-mobilizing mechanisms in the subcutaneous adipose tissue (SCAT) of overweight men and women were ...studied using microdialysis. RESEARCH METHODS AND PROCEDURES: Subjects matched for age, BMI, and physical fitness performed two 30-minute exercise bouts in a randomized fashion: the first test at 30% and 50% of their individual maximal oxygen uptake (VO₂max) and the second test at 30% and 70% of their VO₂max. RESULTS: In both groups, an exercise-dependent increment in extracellular glycerol concentration (EGC) was observed. Whatever the intensity, phentolamine α-adrenergic receptor (AR) antagonist added to a dialysis probe potentiated exercise-induced lipolysis only in men. In a probe containing phentolamine plus propranolol (β-AR antagonist), no changes in EGC occurred when compared with the control probe when exercise was performed at 30% and 50% VO₂max. A significant reduction of EGC (when compared with the control probe) was observed in women at 70% VO₂max. At each exercise power, the plasma non-esterified fatty acid and glycerol concentrations were higher in women. Exercise-induced increase in plasma catecholamine levels was lower in women compared with men. Plasma insulin decreased and atrial natriuretic peptide increased similarly in both groups. DISCUSSION: Overweight women mobilize more lipids (assessed by glycerol) than men during exercise. α₂-Anti-lipolytic effect was functional in SCAT of men only. The major finding is that during low-to-moderate exercise periods (30% and 50% VO₂max), lipid mobilization in SCAT relies less on catecholamine-dependent stimulation of β-ARs than on an increase in plasma atrial natriuretic peptide concentrations and the decrease in plasma insulin.
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