Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

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Influence of low- and high-protein diets on insulin and insulin-like growth factor-1 binding to skeletal muscle and liver in the growing rat

British Journal Of Nutrition ◽

10.1079/bjn19910065 ◽

1991 ◽

Vol 65 (1) ◽

pp. 47-60 ◽

Cited By ~ 26

Author(s):

D. Dardevet ◽

M. Manin ◽

M. Balage ◽

C. Sornet ◽

J. Grizard

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Dietary Protein ◽

Binding Capacity ◽

Plasma Concentrations ◽

Insulin Binding ◽

Metabolic Adaptation ◽

Scatchard Analysis ◽

Insulin Like Growth Factor ◽

Hormone Binding

The influence of protein content of the diet on the plasma concentrations and binding to skeletal muscle and liver of insulin and insulin-like growth factor-1 (IGF-1), was studied in growing rats. Animals with a starting body-weight of 80 g received for an 11 d period isoenergetic diets containing (g/kg dry matter) 155 protein as controls (MP), or 55 (LP) or 300 (HP) protein. Food was offered as six equal meals/d. Daily food intakes provided adequate amounts of energy. Total plasma IGF-1 increased linearly as a function of dietary protein intake. Plasma insulin was lower in the LP than in the MP and HP groups. Hormone binding was studied in wheat-germ agglutinin (WGA) partially purified skeletal muscle receptor preparations. Each 125I-labelled hormone binding was competed for by increasing amounts of homologous and heterologous unlabelled hormone; this displacement needed lower concentrations of homologous than heterologous hormone. When compared with MP-diet feeding, the LP diet resulted in an increased ligand concentration for half-maximal binding. In addition the specific 125I-labelled insulin and 125I-labelled IGF-1 binding increased at all hormone concentrations and, as revealed by Scatchard analysis, the hormone binding capacity also rose (only significant for low-affinity insulin receptors and high-affinity IGF-1 receptors). The HP diet had little effect on hormone binding, except to increase insulin binding at very low insulin concentrations. Hormone binding was further studied in WGA partially purified liver receptor preparations. Those preparations did not exhibit any detectable specific 125I-labelled IGF-1 binding. The specific 125I-labelled insulin binding was not altered by dietary protein level. It is concluded that the increase in skeletal muscle insulin and IGF-1 binding along with a decrease in insulin and IGF-1 in the blood from rats fed on the LP diet, is consistent with the concept of an inverse relationship between plasma hormone and hormone binding. The physiological significance with respect to metabolic adaptation of muscle remains to be established

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Long‐term caloric restriction abrogates the age‐related decline in skeletal muscle aerobic function

The FASEB Journal ◽

10.1096/fj.04-3535fje ◽

2005 ◽

Vol 19 (10) ◽

pp. 1320-1322 ◽

Cited By ~ 54

Author(s):

Russell T. Hepple ◽

David J. Baker ◽

Jan J. Kaczor ◽

Daniel J. Krause

Keyword(s):

Skeletal Muscle ◽

Caloric Restriction ◽

Age Related ◽

Aerobic Function

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Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00347.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. R1059-R1067 ◽

Cited By ~ 64

Author(s):

I. Mark Olfert ◽

Richard A. Howlett ◽

Peter D. Wagner ◽

Ellen C. Breen

Keyword(s):

Skeletal Muscle ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Exercise Training ◽

Metabolic Adaptation ◽

Vascular Endothelial ◽

Vegf Expression ◽

Running Speed ◽

Endothelial Growth Factor ◽

Adaptation To Exercise

We have previously shown, using a Cre-LoxP strategy, that vascular endothelial growth factor (VEGF) is required for the development and maintenance of skeletal muscle capillarity in sedentary adult mice. To determine whether VEGF expression is required for skeletal muscle capillary adaptation to exercise training, gastrocnemius muscle capillarity was measured in myocyte-specific VEGF gene-deleted (mVEGF−/−) and wild-type (WT) littermate mice following 6 wk of treadmill running (1 h/day, 5 days/wk) at the same running speed. The effect of training on metabolic enzyme activity levels and whole body running performance was also evaluated in mVEGF−/− and WT mice. Posttraining capillary density was significantly increased by 59% ( P < 0.05) in the deep muscle region of the gastrocnemius in WT mice but did not change in mVEGF−/− mice. Maximal running speed and time to exhaustion during submaximal running increased by 20 and 13% ( P < 0.05), respectively, in WT mice after training but were unchanged in mVEGF−/− mice. Training led to increases in skeletal muscle citrate synthase (CS) and phosphofructokinase (PFK) activities in both WT and mVEGF−/− mice ( P < 0.05), whereas β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity was increased only in WT mice. These data demonstrate that skeletal muscle capillary adaptation to physical training does not occur in the absence of myocyte-expressed VEGF. However, skeletal muscle metabolic adaptation to exercise training takes place independent of myocyte VEGF expression.

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Regulation of energy intake and mechanisms of metabolic adaptation or maladaptation after caloric restriction

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-020-09565-6 ◽

2020 ◽

Vol 21 (3) ◽

pp. 399-409

Author(s):

Roberto Vettor ◽

Angelo Di Vincenzo ◽

Pietro Maffei ◽

Marco Rossato

Keyword(s):

Caloric Restriction ◽

Energy Intake ◽

Metabolic Adaptation

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9 Resistance to age-related weight gain is associated with stimulation of skeletal muscle mitochondrial oxidative capacity during caloric restriction in young rats

Nutrition Metabolism and Cardiovascular Diseases ◽

10.1016/s0939-4753(05)80009-2 ◽

2005 ◽

Vol 15 ◽

pp. S4

Keyword(s):

Skeletal Muscle ◽

Weight Gain ◽

Caloric Restriction ◽

Oxidative Capacity ◽

Young Rats ◽

Age Related ◽

Mitochondrial Oxidative Capacity ◽

Stimulation Of

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Selective overexpression of Toll-like receptor-4 in skeletal muscle impairs metabolic adaptation to high-fat feeding

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00139.2015 ◽

2015 ◽

Vol 309 (3) ◽

pp. R304-R313 ◽

Cited By ~ 8

Author(s):

Ryan P. McMillan ◽

Yaru Wu ◽

Kevin Voelker ◽

Gabrielle Fundaro ◽

John Kavanaugh ◽

...

Keyword(s):

Skeletal Muscle ◽

High Fat Diet ◽

Whole Body ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

Chow Diet ◽

Toll Like Receptor ◽

High Fat ◽

Toll Like Receptor 4 ◽

Fat Feeding

Toll-like receptor-4 (TLR-4) is elevated in skeletal muscle of obese humans, and data from our laboratory have shown that activation of TLR-4 in skeletal muscle via LPS results in decreased fatty acid oxidation (FAO). The purpose of this study was to determine whether overexpression of TLR-4 in skeletal muscle alters mitochondrial function and whole body metabolism in the context of a chow and high-fat diet. C57BL/6J mice (males, 6–8 mo of age) with skeletal muscle-specific overexpression of the TLR-4 (mTLR-4) gene were created and used for this study. Isolated mitochondria and whole muscle homogenates from rodent skeletal muscle (gastrocnemius and quadriceps) were investigated. TLR-4 overexpression resulted in a significant reduction in FAO in muscle homogenates; however, mitochondrial respiration and reactive oxygen species (ROS) production did not appear to be affected on a standard chow diet. To determine the role of TLR-4 overexpression in skeletal muscle in response to high-fat feeding, mTLR-4 mice and WT control mice were fed low- and high-fat diets for 16 wk. The high-fat diet significantly decreased FAO in mTLR-4 mice, which was observed in concert with elevated body weight and fat, greater glucose intolerance, and increase in production of ROS and cellular oxidative damage compared with WT littermates. These findings suggest that TLR-4 plays an important role in the metabolic response in skeletal muscle to high-fat feeding.

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