RESUMO
The Ala allele of PPARG Pro12Ala ( rs1801282 ) is associated with greater improvements to the glucose metabolism in exercise studies, but whether this extends to peripheral insulin sensitivity is unknown. Our objective was to investigate the effect of PPARG Pro12Ala on exercise-induced changes in peripheral insulin sensitivity. A total of 124 (91 Pro homozygotes and 33 Ala carriers) previously physically inactive healthy young men and women with overweight or class 1 obesity who completed a 12 wk aerobic exercise intervention were included in the analysis. All participants underwent a hyperinsulinemic euglycemic clamp before and after the 12 wk intervention. The prescribed exercise frequency was 5-7 days/wk, and the exercise energy expenditure was 2,100 4,200 kcal/wk for men and 1,600 kcal/wk for women. Insulin sensitivity improved significantly in both genotype groups. However, Ala carriers had a 1.13-fold (95% confidence interval 1.01; 1.26, P = 0.032) greater improvement in insulin sensitivity from baseline compared with Pro homozygotes. Our data support that PPARG Pro12Ala modifies the effect of aerobic exercise on peripheral insulin sensitivity.
Assuntos
Exercício Físico/fisiologia , Resistência à Insulina/fisiologia , PPAR gama/metabolismo , Adulto , Alelos , Índice de Massa Corporal , Metabolismo Energético/fisiologia , Feminino , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/fisiopatologia , Adulto JovemRESUMO
Obese individuals are characterized by low circulating adiponectin concentrations and an increased number of macrophages in adipose tissue, which is believed to be causally associated with chronic low-grade inflammation and insulin resistance. Regular physical exercise decreases overall morbidity in obese subjects, which may be due to modulations of inflammatory pathways. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss, and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men. Weight loss and endurance training per se decreased whole body fat percentage in an additive manner. No intervention-induced changes were observed for plasma total adiponectin. Surprisingly, endurance training, irrespectively of any associated weight loss, shifted the adiponectin multimer distribution toward a lower molecular weight (21% decrease in HMW/LMW, P = 0.015), whereas diet-induced weight loss shifted the distribution toward a higher molecular weight (42% increase in HMW/MMW, P < 0.001). Furthermore, endurance training per se increased the number of anti-inflammatory CD163⺠macrophages [from 12.7 ± 2.1 (means ± SE) to 16.1 ± 3.1 CD163⺠cells/100 adipocytes, P = 0.013], whereas diet-induced weight loss tended to decrease CD68⺠macrophages in subcutaneous abdominal adipose tissue. Thus regular physical exercise influences systemic and adipose tissue inflammatory pathways differently than diet-induced weight loss in younger, moderately overweight men. Our data suggest that some of the health benefits of a physically active lifestyle may occur through modulations of anti- rather than pro-inflammatory pathways in young, overweight men.
Assuntos
Adiponectina/sangue , Tecido Adiposo/patologia , Macrófagos/patologia , Sobrepeso/fisiopatologia , Sobrepeso/reabilitação , Resistência Física , Redução de Peso , Tecido Adiposo/fisiopatologia , Adulto , Humanos , Masculino , Aptidão Física , Multimerização Proteica , Resultado do TratamentoRESUMO
Efficient lipid digestion in formula-fed infants is required to ensure the availability of fatty acids for normal organ development. Previous studies suggest that the efficiency of lipid digestion may depend on whether lipids are emulsified with soy lecithin or fractions derived from bovine milk. This study, therefore, aimed to determine whether emulsification with bovine milk-derived emulsifiers or soy lecithin (SL) influenced lipid digestion in vitro and in vivo. Lipid digestibility was determined in vitro in oil-in-water emulsions using four different milk-derived emulsifiers or SL, and the ultrastructural appearance of the emulsions was assessed using electron microscopy. Subsequently, selected emulsions were added to a base diet and fed to preterm neonatal piglets. Initially, preterm pigs equipped with an ileostomy were fed experimental formulas for seven days and stoma output was collected quantitatively. Next, lipid absorption kinetics was studied in preterm pigs given pure emulsions. Finally, complete formulas with different emulsions were fed for four days, and the post-bolus plasma triglyceride level was determined. Milk-derived emulsifiers (containing protein and phospholipids from milk fat globule membranes and extracellular vesicles) showed increased effects on fat digestion compared to SL in an in vitro digestion model. Further, milk-derived emulsifiers significantly increased the digestion of triglyceride in the preterm piglet model compared with SL. Ultra-structural images indicated a more regular and smooth surface of fat droplets emulsified with milk-derived emulsifiers relative to SL. We conclude that, relative to SL, milk-derived emulsifiers lead to a different surface ultrastructure on the lipid droplets, and increase lipid digestion.
Assuntos
Absorção Fisiológica , Emulsões/farmacologia , Comportamento Alimentar , Fórmulas Infantis , Leite/química , Triglicerídeos/metabolismo , Absorção Fisiológica/efeitos dos fármacos , Animais , Bovinos , Digestão , Ácidos Graxos/metabolismo , Fezes , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Cinética , Lipólise/efeitos dos fármacos , Tamanho da Partícula , Estômago/fisiologia , SuínosRESUMO
The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108 ng x 100 g(-1) x min(-1) (P < 0.05), with no significant change in the control subjects, but there was no training-induced increase in the release of BDNF during exercise. Additionally, eight mice completed a 5-wk treadmill running training protocol that increased the BDNF mRNA expression in the hippocampus (4.5 + or - 1.6 vs. 1.4 + or - 1.1 mRNA/ssDNA; P < 0.05), but not in the cerebral cortex (4.0 + or - 1.4 vs. 4.6 + or - 1.4 mRNA/ssDNA) compared with untrained mice. The increased BDNF expression in the hippocampus and the enhanced release of BDNF from the human brain following training suggest that endurance training promotes brain health.
Assuntos
Química Encefálica/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Resistência Física/fisiologia , Aptidão Física/fisiologia , Adulto , Limiar Anaeróbio/fisiologia , Animais , Córtex Cerebral/metabolismo , Circulação Cerebrovascular/fisiologia , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Artéria Cerebral Média/fisiologia , Condicionamento Físico Animal/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Descanso/fisiologiaRESUMO
Both exercise training and weight loss reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 wk of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C). Equal energetic deficits (-600 kcal/day) were prescribed by exercise for T and caloric restriction for D. T-iD completed similar exercise but remained in energy balance due to the dietary replacement of calories expended during exercise. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)B and A1, pre-ß-HDL, and susceptibility of LDL-C to oxidation were measured. Body weight was reduced similarly between T (-5.9 ± 0.7 kg) and D (-5.2 ± 0.8 kg), whereas T-iD (-1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. Plasma TC, LDL-C, and apolipoprotein B were reduced in T compared with C ( P < 0.001 for both), but this was not observed for D ( P > 0.17). Changes in TC and LDL-C were associated with changes in body weight and body fat ( P < 0.01). In T-iD, increases in HDL-C and apolipoprotein A1 were observed ( P < 0.001). In conclusion, an exercise-induced decline in body weight reduces proatherogenic apoB-containing lipoproteins, whereas exercise compensated by energy intake increases the key component of reverse cholesterol transport, i.e., apoA1-containing HDL-C. NEW & NOTEWORTHY Exercise has additive effects in lowering plasma lipoprotein particles to diet-induced weight loss in individuals with increased cardiovascular risk. In the present study, we investigated whether training per se would have beneficial cardiovascular effects. We found that 3 mo of exercise-induced weight loss reduced proatherogenic lipoproteins, whereas endurance training without weight loss improved factors involved in reverse cholesterol transport in a group of overweight sedentary men.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Exercício Físico , Sobrepeso/complicações , Redução de Peso , Adulto , Apolipoproteínas B/sangue , Composição Corporal , Restrição Calórica , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/prevenção & controle , Humanos , Lipoproteínas/sangue , Masculino , Aptidão Física , Fatores de RiscoRESUMO
INTRODUCTION: The cardiovascular risk marker tissue plasminogen activator antigen (t-PA:Ag) can be reduced by long-term exercise interventions, but it is unknown, whether this is due to the weight loss induced by physical activity or due to the physical activity per se. MATERIALS AND METHODS: This was tested in 60 healthy, younger (20-40years), overweight (BMI: 25-30kg/m2) men randomly assigned to 12weeks of intervention in one of four groups: training (T); energy-reduced diet (D); training and increased diet (T-iD); sedentary lifestyle and unchanged diet (controls, C). Fasting blood samples were obtained before and after 12weeks of intervention and analyzed for plasma t-PA:Ag. RESULTS: Body weight was reduced in groups T and D. We observed a decrease in t-PA:Ag from baseline to 12weeks in all three exercise and diet intervention groups, and no change in the control group. A between-group difference in t-PA:Ag was observed at 12weeks (p=0.001), and this was due to lower values in T (p=0.0005), D (p=0.005) and T-iD (p=0.009) compared with the control group. Total body fat mass was reduced in all three exercise groups, and we observed a positive correlation between changes in t-PA:Ag and changes in intra-abdominal and subcutaneous adipose tissue volume. CONCLUSIONS: Our results demonstrate that t-PA:Ag was reduced in all three intervention groups. This suggests that 12weeks of endurance training per se, irrespective of concomitant weight loss, beneficially affects cardiovascular risk in healthy, younger, overweight men.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Sobrepeso/complicações , Sobrepeso/terapia , Ativador de Plasminogênio Tecidual/sangue , Adulto , Exercício Físico , Terapia por Exercício , Humanos , Masculino , Sobrepeso/sangue , Resistência Física , Comportamento Sedentário , Redução de Peso , Adulto JovemRESUMO
Endurance training increases peak fat oxidation (PFO) during exercise, but whether this is independent of changes in body weight is not known. The aim of the present study was to investigate the effects of endurance training with or without weight loss or a diet-induced weight loss on PFO and on key skeletal muscle mitochondrial proteins involved in fat oxidation. Sixty moderately overweight, sedentary but otherwise healthy men were randomized to 12 wk of training (T), diet (D), training and increased caloric intake (T-iD), or continuous sedentary control (C). Isoenergetic deficits corresponding to 600 kcal/day were comprised of endurance exercise for T and caloric restriction for D. T-iD completed similar training but was not in 600 kcal deficit because of dietary replacement. PFO and the exercise intensity at which this occurred (FatMax) were measured by a submaximal exercise test and calculated by polynomial regression. As intended by study design, a similar weight loss was observed in T (-5.9 ± 0.7 kg) and D (-5.2 ± 0.8 kg), whereas T-iD (-1.0 ± 0.5 kg) and C (0.1 ± 0.6 kg) remained weight stable. PFO increased to a similar extent with 42% in T [0.16 g/min; 95% confidence intervals (CI): 0.02; 0.30, P = 0.02] and 41% in T-iD (0.16 g/min; 95% CI: 0.01; 0.30, P = 0.04) compared with C, but did not increase in D (P = 0.96). In addition, the analysis of covariance showed that changes in both PFO (0.10 g/min; 95% CI: 0.03; 0.17, P = 0.03) and FatMax (6.3% VÌo2max; 95% CI: 1.4; 11.3, P < 0.01) were independently explained by endurance training. In conclusion, endurance training per se increases PFO in moderately overweight men.
Assuntos
Tecido Adiposo/metabolismo , Terapia por Exercício/métodos , Sobrepeso/fisiopatologia , Sobrepeso/terapia , Resistência Física , Redução de Peso/fisiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Condicionamento Físico Humano/métodos , Resultado do TratamentoRESUMO
Skeletal muscle energy metabolism has been a research focus of physiologists for more than a century. Yet, how the use of intramuscular carbohydrate and lipid energy stores are coordinated during different types of exercise remains a subject of debate. Controversy arises from contradicting data from numerous studies, which used different methodological approaches. Here we review the "pros and cons" of previously used histochemical methods and describe an optimized method to ensure the preservation and specificity of detection of both intramyocellular carbohydrate and lipid stores. For optimal preservation of muscle energy stores, air drying cryosections or cycles of freezing-thawing need to be avoided. Furthermore, optimization of the imaging settings in order to specifically image intracellular lipid droplets stained with oil red O or Bodipy-493/503 is shown. When co-staining lipid droplets with associated proteins, Bodipy-493/503 should be the dye of choice, since oil red O creates precipitates on the lipid droplets blocking the light. In order to increase the specificity of glycogen stain, an antibody against glycogen is used. The resulting method reveals the existence of two metabolically distinct myosin heavy chain I expressing fibers: I-1 fibers have a smaller crossectional area, a higher density of lipid droplets, and a tendency to lower glycogen content compared to I-2 fibers. Type I-2 fibers have similar lipid content than IIA. Exhaustive exercise lead to glycogen depletion in type IIA and IIX fibers, a reduction in lipid droplets density in both type I-1 and I-2 fibers, and a decrease in the size of lipid droplets exclusively in type I-1 fibers.
Assuntos
Exercício Físico/fisiologia , Glicogênio/metabolismo , Lipídeos/fisiologia , Fibras Musculares de Contração Lenta/classificação , Fibras Musculares de Contração Lenta/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Músculo Quadríceps/metabolismo , Adulto , Biópsia , Metabolismo Energético , Humanos , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Músculo Quadríceps/cirurgiaRESUMO
Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy-reduced diet in 48 sedentary, moderately overweight men who completed a 12-week intervention program of training (T), energy-reduced diet (D), training and increased diet (T-iD), or control (C). An energy deficit of 600 kcal/day was induced by endurance training or diet in T and D and a similar training regimen plus an increased dietary intake of 600 kcal/day defined the T-iD group. Primary end point was insulin sensitivity as evaluated by HOMA-IR (mainly reflecting hepatic insulin sensitivity) and hyperinsulinemic, isoglycemic clamps (primarily reflecting peripheral insulin sensitivity). Body mass decreased in T and D by 5.9 ± 0.7 and 5.3 ± 0.7 kg, respectively, whereas T-iD and C remained weight stable. Total and abdominal fat mass were reduced in an additive manner in the T-iD, D, and T groups by 1.9 ± 0.3/0.2 ± 0.1, 4.4 ± 0.7/0.5 ± 0.1, and 7.7 ± 0.8/0.9 ± 0.1 kg, respectively. HOMA-IR was improved in T, D, and T-iD, whereas insulin-stimulated glucose clearance and suppression of plasma nonesterified fatty acids (NEFAs) were increased only in the two training groups. Thus, loss of fat mass (diet or training induced) improves hepatic insulin sensitivity, whereas peripheral insulin sensitivity in skeletal muscle and adipose tissue is increased by endurance training only. This demonstrates that endurance training per se increases various metabolic health parameters and that endurance training should preferably always be included in any intervention regimen for improving metabolic health in moderately overweight men.
Assuntos
Glicemia/metabolismo , Terapia por Exercício , Hemoglobinas Glicadas/metabolismo , Resistência à Insulina , Sobrepeso/metabolismo , Resistência Física , Adulto , Análise de Variância , Biomarcadores/metabolismo , Distribuição da Gordura Corporal , Índice de Massa Corporal , Dieta Redutora , Técnica Clamp de Glucose , Homeostase , Humanos , Masculino , Sobrepeso/dietoterapia , Sobrepeso/reabilitação , Comportamento SedentárioRESUMO
Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated dephosphorylation at sites 2+2a, 3a, and 3a + 3b. Furthermore, we report the existence of several glycogen metabolism regulatory mechanisms based on GS intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to GS site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. On the other hand, when phosphorylated at sites 2+2a, GS is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. Finally, we verify the existence in human vastus lateralis muscle of the previously reported mechanism of glycogen metabolism regulation in rabbit tibialis anterior muscle. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, GS is associated with spherical structures at the I-band of sarcomeres.