Effects of acute and chronic hindlimb suspension on sensitivity and responsiveness to insulin in the rat soleus muscle

Langfort, Józef; Zernicka, E; Mayet-Sornay, Marie Hélène; Dubaniewicz, Anna; Desplanches, Dominique

doi:10.1139/o96-059

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…Increased reliance on glucose and a corresponding decrease in fatty acid oxidation in skeletal muscle [60, 61] has also been found in PCOS women, and associated with decreased oxidative metabolism [62] in tandem with decreased mitochondrial respiration [63]. In the latter PCOS-associated metabolic inflexibility, diminished gene expression regulating fatty acid oxidation and lipid metabolism, combined with increased expression of glycolytic enzymes [64, 65], may result in reduced glycogen synthesis coincident with increased reliance on glucose, rather than lipid, as an energy source [61, 66, 67]. An additional recent study, however, also employing changes in RQ values during a hyperinsulinemic-euglycemic clamp, found evidence of metabolic inflexibility in overweight and obese women that was not influenced by the presence of PCOS [68].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

Whigham¹,

Bütz²,

Dashti³

et al. 2014

CMB

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Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.

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Section: Discussionmentioning

confidence: 99%

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

Whigham¹,

Bütz²,

Dashti³

et al. 2014

CMB

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“…Overall, our data confirm the expected significant elevation of glycolytic mRNAs, concomitantly with mRNAs encoding glut‐4 associated factors, plus a moderate augmentation of mRNAs involved in oxidative phosphorylation with a drop in mRNAs of proteins involved in the import of fatty acids. In response to HS, increased insulin sensitivity, as well as increased Glut‐4 and associated glucose transport that persists for at least 5 weeks (61), have been established for rat m. soleus (25–27, 62–64). Although the complex system of glucose homeostasis is regulated at many levels (65), the increased mRNA of the glut‐4 vesicle associated VAMP3, M6P/IGFR2, and IRAP indicates that an increase in the glut‐4 vesicle pool could contribute to the increased glucose transport capacity that is associated with HS (63, 66, 67).…”

Section: Discussionmentioning

confidence: 99%

Prolonged unloading of rat soleus muscle causes distinct adaptations of the gene profile

Wittwer¹,

Flück²,

Hoppeler³

et al. 2002

FASEB j.

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Using commercially available microarray technology, we investigated a series of transcriptional adaptations caused by atrophy of rat m. soleus due to 35 days of hindlimb suspension. We detected 395 out of 1,200 tested transcripts, which reflected 1%-5% of totally expressed genes. From various cellular functional pathways, we detected multiple genes that spanned a 200-fold range of gene expression levels. Statistical analysis combining L1 regression with the sign test based on the conservative Bonferroni correction identified 105 genes that underwent transcriptional adaptations with atrophy. Generally, expressional changes were discrete (<50%) and pointed in the same direction for genes belonging to the same cellular functional units. In particular, a distinct expressional adaptation of genes involved in fiber transformation; that is, metabolism, protein turnover, and cell regulation were noted and matched to corresponding transcriptional changes in nutrient trafficking. Expressional changes of extracellular proteases, and of genes involved in nerve-muscle interaction and excitation-contraction coupling identify previously not recognized adaptations that occur in atrophic m. soleus. Considerations related to technical and statistical aspects of the array approach for profiling the skeletal muscle genome and the impact of observed novel adaptations of the m. soleus transcriptome are put into perspective of the physiological adaptations occurring with muscular atrophy.

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“…Skeletal muscle metabolism undergoes an adaptive response to decreased usage as shown in various models of muscle disuse, such as hindlimb suspension, space flight, and bed rest. Globally, this adaptive response is characterized by a reduction of fatty acid utilization and increased glucose utilization in rodent and human muscles (25,54,158,315,478). This shift in fuel metabolism from lipids toward glucose is related to augmented expression and activity of several glycolytic enzymes, such as PFK, hexokinase, and pyruvate kinase (47,96,536,558,574,646), and decreased expression and activity of enzymes of FAO (227,536,558,646).…”

Section: Metabolic and Functional Diversity Of Skeletal Musclementioning

confidence: 99%

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

Neels

Grimaldi

2014

Physiological Reviews

148

146

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The peroxisome proliferator-activated receptors, PPARα, PPARβ, and PPARγ, are a family of transcription factors activated by a diversity of molecules including fatty acids and fatty acid metabolites. PPARs regulate the transcription of a large variety of genes implicated in metabolism, inflammation, proliferation, and differentiation in different cell types. These transcriptional regulations involve both direct transactivation and interaction with other transcriptional regulatory pathways. The functions of PPARα and PPARγ have been extensively documented mainly because these isoforms are activated by molecules clinically used as hypolipidemic and antidiabetic compounds. The physiological functions of PPARβ remained for a while less investigated, but the finding that specific synthetic agonists exert beneficial actions in obese subjects uplifted the studies aimed to elucidate the roles of this PPAR isoform. Intensive work based on pharmacological and genetic approaches and on the use of both in vitro and in vivo models has considerably improved our knowledge on the physiological roles of PPARβ in various cell types. This review will summarize the accumulated evidence for the implication of PPARβ in the regulation of development, metabolism, and inflammation in several tissues, including skeletal muscle, heart, skin, and intestine. Some of these findings indicate that pharmacological activation of PPARβ could be envisioned as a therapeutic option for the correction of metabolic disorders and a variety of inflammatory conditions. However, other experimental data suggesting that activation of PPARβ could result in serious adverse effects, such as carcinogenesis and psoriasis, raise concerns about the clinical use of potent PPARβ agonists.

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Effects of acute and chronic hindlimb suspension on sensitivity and responsiveness to insulin in the rat soleus muscle

Cited by 10 publications

References 22 publications

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

Prolonged unloading of rat soleus muscle causes distinct adaptations of the gene profile

Physiological Functions of Peroxisome Proliferator-Activated Receptor β

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