RESUMEN
BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) appears to have impaired effect on subcutaneous abdominal adipose tissue metabolism in obese subjects. The aim of the present study was to examine whether weight loss may reverse the impaired effect of GIP on subcutaneous abdominal adipose tissue in obese subjects. METHODS: Five obese males participated in a 12-week weight loss program, which consisted of caloric restriction (800 Cal day(-)(1)) followed by 4 weeks of weight-maintenance diet. Before and after weight loss, subcutaneous adipose tissue lipid metabolism was studied by conducting regional measurements of arterio-venous plasma concentrations of metabolites and blood flow (adipose tissue blood flow, ATBF) across a segment of the abdominal adipose tissue in the fasting state and during GIP infusion (1.5 pmol kg(-)(1 )min(-)(1)) in combination with a hyperinsulinemic-hyperglycemic clamp. RESULTS: After weight loss (7.5±0.8 kg), glucose tolerance and insulin sensitivity increased significantly as expected. No significant differences were seen in basal ATBF before (1.3±0.4 ml min(-1) 100 g tissue(-1)) and after weight loss (2.1±0.4 ml min(-1) 100 g tissue)(-1); however, a tendency to increase was seen. After weight loss, GIP infusion increased ATBF significantly (3.2±0.1 ml min(-1) 100 g tissue(-1)) whereas there was no increase before weight loss. Triacylglycerol (TAG) uptake did not change after weight loss. Baseline free fatty acid (FFA) and glycerol output increased significantly after weight loss, P<0.001. During the clamp period, FFA and glycerol output declined significantly, P<0.05, with no differences before and after weight loss. Weight loss increased glucose uptake and decreased FFA/glycerol ratio during the clamp period, P<0.05. CONCLUSIONS: In obese subjects, weight loss, induced by calorie restriction, improves the blunted effect of GIP on subcutaneous abdominal adipose tissue metabolism.
Asunto(s)
Polipéptido Inhibidor Gástrico/metabolismo , Obesidad/terapia , Grasa Subcutánea Abdominal/metabolismo , Pérdida de Peso , Adulto , Glucemia/metabolismo , Composición Corporal , Índice de Masa Corporal , Restricción Calórica , Dieta , Ayuno , Ácidos Grasos no Esterificados/metabolismo , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Triglicéridos/metabolismo , Programas de Reducción de PesoRESUMEN
Sustained improvements in cardiovascular fitness and body composition after lifestyle interventions are challenging. The present study investigated whether changes in cardiovascular fitness and body composition were maintained for up to 1 year after similar exercise-induced (T) or diet-induced weight loss (D) or exercise without weight loss (T-iD) in overweight sedentary men. Six and 12 months after the interventions, we measured cardiovascular fitness and body composition. Cardiovascular fitness was higher at both 6- (3.2±1.5 ml O2/kg/min, P=0.053) and 12-month follow-up (3.9±1.4 ml O2/kg/min, P=0.049) compared with pre-intervention in T. Fat mass (-3.0±1.2 kg, P=0.04) and abdominal fat (-3.6±1.5%, P=0.04) were lower within T at 12-month follow-up compared with pre-intervention. This did not occur in D (P>0.13) or T-iD (P>0.14), although body weight was lower in D (-2.5±2.2 kg, P=0.09). This study showed that fitness and fatness were not returned to pre-intervention levels 1 year after a 3-month exercise-induced weight-loss intervention.
Asunto(s)
Composición Corporal , Enfermedades Cardiovasculares/prevención & control , Dieta Reductora , Obesidad Mórbida/terapia , Consumo de Oxígeno , Adulto , Enfermedades Cardiovasculares/fisiopatología , Terapia por Ejercicio , Humanos , Masculino , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Maternal obesity is associated with increased risk of metabolic dysfunction in the offspring. It is not clear whether it is the metabolic changes or chronic low-grade inflammation in the obese state that causes this metabolic programming. We therefore investigated whether low-grade inflammation was present in obese dams compared with controls dams at gestation day 18 (GD18). METHODS: Female mice were fed either a standard chow diet or a highly palatable obesogenic diet for 6 weeks before conception. Mice were either kileed before mating (n=12 in each group) or on GD18 (n=8 in each group). Blood and tissues were collected for analysis. RESULTS: The obesogenic diet increased body weight and decreased insulin sensitivity before conception, while there was no difference between the groups at GD18. Local inflammation was assayed by macrophage count in adipose tissue (AT) and liver. Macrophage count in the AT was increased significantly by the obesogenic diet, and the hepatic count also showed a tendency to increased macrophage infiltration before gestation. This was further supported by a decreased population of monocytes in the blood of the obese animals, which suggested that monocytes are being recruited from the blood to the liver and AT in the obese animals. Gestation reversed macrophage infiltration, such that obese dams showed a lower AT macrophage count at the end of gestation compared with pre-pregnancy obese mice, and there were no longer a tendency toward increased hepatic macrophage count. Placental macrophage count was also similar in the two groups. CONCLUSION: At GD18, obese dams were found to have similar macrophage infiltration in placenta, AT and liver as lean dams, despite an incipient infiltration before gestation. Thus, the obesity-induced inflammation was reversed during gestation.
Asunto(s)
Desarrollo Fetal , Inflamación/patología , Hígado/metabolismo , Síndrome Metabólico/patología , Obesidad/patología , Efectos Tardíos de la Exposición Prenatal/patología , Animales , Modelos Animales de Enfermedad , Femenino , Desarrollo Fetal/inmunología , Citometría de Flujo , Inmunohistoquímica , Inflamación/inmunología , Síndrome Metabólico/inmunología , Ratones , Ratones Endogámicos C57BL , Obesidad/inmunología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inmunología , Aumento de Peso/inmunologíaRESUMEN
Human muscle is studied during glycogen depletion and repletion to understand the influence of exercise and muscle glycogen on total ceramide content. In addition, fiber-type-specific ceramide storage is investigated. Ten healthy males (26.4 +/- 0.9 years, BMI 24.4 +/- 0.7 kg m(-2) and VO2max 57 +/- 2 mL O2 min(-1) kg(-1)) participated in the study. On the first day, one leg was glycogen-depleted (DL) by exhaustive intermittent exercise followed by low carbohydrate diet. Next day, in the overnight fasted condition, muscle biopsies were excised from vastus lateralis before and after exhaustive exercise from both DL and control leg (CL). Muscle glycogen was analyzed biochemically and total muscle ceramide content by 2D quantitative lipidomic approach. Furthermore, fiber-type ceramide content was determined by fluorescence immunohistochemistry. Basal muscle glycogen was decreased (P < 0.05) with 50 +/- 6% in DL versus CL. After exhaustive exercise, muscle glycogen was similar in CL and DL 139 +/- 38 and 110 +/- 31 mmol kg(-1), respectively. Total muscle ceramide 58 +/- 1 pmol mg(-1) was not influenced by glycogen or exercise. Ceramide content was consistently higher (P < 0.001) in type I than in type II muscle fibers. In conclusion, human skeletal muscle, ceramide content is higher in type I than in type II. Despite rather large changes in muscle glycogen induced by prior depletion, exercise to exhaustion and repletion, total muscle ceramide concentration remained unchanged.
Asunto(s)
Ceramidas/metabolismo , Glucógeno/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Adulto , Biopsia , Ejercicio Físico/fisiología , Humanos , Masculino , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Resistencia Física/fisiologíaRESUMEN
OBJECTIVE: To elucidate if fat oxidation at rest predicts peak fat oxidation during exercise and/or metabolic phenotype in moderately overweight, sedentary men. DESIGN: Cross-sectional study. SUBJECTS: We measured respiratory exchange ratio (RER) at rest in 44 moderately overweight, normotensive and normoglycemic men and selected 8 subjects with a low RER (L-RER, body mass index (BMI): 27.9+/-0.9 kg m(-2), RER: 0.76+/-0.02) and 8 with a high RER (H-RER; BMI 28.1+/-1.1 kg m(-2), RER: 0.89+/-0.02). After an overnight fast, a venous blood sample was obtained and a graded exercise test was performed. Fat oxidation during exercise was quantified using indirect calorimetry. RESULTS: Peak fat oxidation during exercise was higher in L-RER than in H-RER (0.333+/-0.096 vs 0.169+/-0.028 g min(-1); P<0.01) and occurred at a higher relative intensity (36.2+/-6.6 vs 28.2+/-3.1% VO(2max), P<0.05). Using the International Diabetes Federation criteria, we found that there was a lower accumulation of metabolic risk factors in L-RER than in H-RER (1.6 vs 3.5, P=0.028), and no subjects in L-RER and four of eight subjects in H-RER had the metabolic syndrome. Resting RER was positively correlated with plasma triglycerides (P<0.01) and negatively with plasma free fatty acids (P<0.05), and peak fat oxidation during exercise was positively correlated with plasma free fatty acid concentration at rest (P<0.05). CONCLUSION: A low RER at rest predicts a high peak fat oxidation during exercise and a healthy metabolic phenotype in moderately overweight, sedentary men.
Asunto(s)
Metabolismo Basal/fisiología , Metabolismo de los Lípidos/fisiología , Sobrepeso , Consumo de Oxígeno/fisiología , Adulto , Índice de Masa Corporal , Calorimetría Indirecta , Estudios Transversales , Ejercicio Físico/fisiología , Ayuno/fisiología , Ácidos Grasos no Esterificados/sangre , Humanos , Metabolismo de los Lípidos/genética , Masculino , Sobrepeso/metabolismo , Sobrepeso/fisiopatología , Oxidación-Reducción , Consumo de Oxígeno/genética , Fenotipo , Descanso/fisiología , Conducta Sedentaria , Triglicéridos/sangreRESUMEN
Endurance training improves muscular and cardiovascular fitness, but the effect on cerebral oxygenation and metabolism remains unknown. We hypothesized that 3 mo of endurance training would reduce cerebral carbohydrate uptake with maintained cerebral oxygenation during submaximal exercise. Healthy overweight males were included in a randomized, controlled study (training: n = 10; control: n = 7). Arterial and internal jugular venous catheterization was used to determine concentration differences for oxygen, glucose, and lactate across the brain and the oxygen-carbohydrate index [molar uptake of oxygen/(glucose + (1/2) lactate); OCI], changes in mitochondrial oxygen tension (DeltaP(Mito)O(2)) and the cerebral metabolic rate of oxygen (CMRO(2)) were calculated. For all subjects, resting OCI was higher at the 3-mo follow-up (6.3 +/- 1.3 compared with 4.7 +/- 0.9 at baseline, mean +/- SD; P < 0.05) and coincided with a lower plasma epinephrine concentration (P < 0.05). Cerebral adaptations to endurance training manifested when exercising at 70% of maximal oxygen uptake (approximately 211 W). Before training, both OCI (3.9 +/- 0.9) and DeltaP(Mito)O(2) (-22 mmHg) decreased (P < 0.05), whereas CMRO(2) increased by 79 +/- 53 micromol x 100 x g(-1) min(-1) (P < 0.05). At the 3-mo follow-up, OCI (4.9 +/- 1.0) and DeltaP(Mito)O(2) (-7 +/- 13 mmHg) did not decrease significantly from rest and when compared with values before training (P < 0.05), CMRO(2) did not increase. This study demonstrates that endurance training attenuates the cerebral metabolic response to submaximal exercise, as reflected in a lower carbohydrate uptake and maintained cerebral oxygenation.
Asunto(s)
Encéfalo/metabolismo , Ejercicio Físico , Sobrepeso/metabolismo , Consumo de Oxígeno , Oxígeno/sangre , Resistencia Física , Adaptación Fisiológica , Adulto , Glucemia/metabolismo , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Epinefrina/sangre , Tolerancia al Ejercicio , Hemodinámica , Humanos , Ácido Láctico/sangre , Masculino , Mitocondrias/metabolismo , Norepinefrina/sangre , Sobrepeso/diagnóstico por imagen , Sobrepeso/fisiopatología , Factores de Tiempo , Ultrasonografía Doppler TranscranealRESUMEN
During whole-body exercise, peak fat oxidation occurs at a moderate intensity. This study investigated whole-body peak fat oxidation in untrained and trained subjects, and the presence of a relation between skeletal muscle oxidative enzyme activity and whole-body peak fat oxidation. Healthy male subjects were recruited and categorized into an untrained (N=8, VO(2max) 3.5+/-0.1 L/min) and a trained (N=8, VO(2max) 4.6+/-0.2 L/min) group. Subjects performed a graded exercise test commencing at 60 W for 8 min followed by 35 W increments every 3 min. On a separate day, muscle biopsies were obtained from vastus lateralis and a 3 h bicycle exercise test was performed at 58% of VO(2max). Whole-body fat oxidation was calculated during prolonged and graded exercise from the respiratory exchange ratio using standard indirect calorimetry equations. Based on the graded exercise test, whole-body peak fat oxidation was determined. The body composition was determined by DEXA. Whole-body peak fat oxidation (250+/-25 and 462+/-33 mg/min) was higher (P<0.05) and occurred at a higher (P<0.05) relative workload (43.5+/-1.8% and 49.9+/-1.2% VO(2max)) in trained compared with untrained subjects, respectively. Muscle citrate synthase activity and beta-hydroxy-acyl-CoA-dehydrogenase activity were higher (49% and 35%, respectively, P<0.05) in trained compared with untrained subjects. Both lean body mass and maximal oxygen uptake were significantly correlated to whole-body peak fat oxidation (r(2)=0.57, P<0.001), but leg muscle oxidative capacity was not correlated to whole-body peak fat oxidation. In conclusion, whole-body peak fat oxidation occurred at a higher relative exercise load in trained compared with untrained subjects. Whole-body peak fat oxidation was not significantly related to leg muscle oxidative capacity, but was related to lean body mass and maximal oxygen uptake. This may suggest that leg muscle oxidative activity is not the main determinant of whole-body peak fat oxidation.