scholarly journals Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet

2021 ◽  
Author(s):  
Huimei Fan ◽  
YanHong Li ◽  
Jie Wang ◽  
Jiahao Shao ◽  
Tao Tang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Muscle Metabolism ◽  
Principal Component ◽  
Least Square ◽  
Rabbit Skeletal Muscle ◽  
Untargeted Metabolomics ◽  
High Fat ◽  
Skeletal Muscle Metabolism

Abstract Background: Type 2 diabetes and metabolic syndrome caused by a high fat diet (HFD) have become public health problems around the world. These diseases are characterized by disrupted mitochondrial oxidation and insulin resistance in skeletal muscle, but the mechanism is not clear. Therefore, this study aims to reveal how a high-fat diet induces skeletal muscle metabolism disorder.Methods：Sixteen weaned rabbits were randomly divided into two groups, one fed with a standard normal diet (SND) and another one fed a HFD for five weeks. Skeletal muscle tissue samples were extracted from each rabbit at the end of the 5-week trial. An untargeted metabolomics profiling was performed using ultraperformance liquid chromatography combined with mass spectrometry (UHPLC-MS/MS).Results: The HFD significantly altered the expression levels of phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone in skeletal muscle. Principal component analysis (PCA) and least square discriminant analysis (PLS-DA) indicated that rabbit skeletal muscle metabolism in the HFD group was significantly up-regulated compared with that of the SND group. Among the 43 skeletal muscle metabolites in the HFD group, phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone were identified as biomarkers for skeletal muscle metabolic diseases, and may also serve as potential physiological targets for related diseases in the future.Conclusion: The untargeted metabolomics analysis revealed that a HFD altered the rabbit skeletal muscle metabolism of phospholipids, carnitine, amino acids, and steroids. Notably, phospholipids, LCACs, histidine, carnosine and tetrahydrocorticosterone blocked the oxidative ability of mitochondria, and disturbed the oxidative ability of glucose and the fatty acid-glucose cycle in rabbit skeletal muscle.

scholarly journals Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1722
Author(s):  
Huimei Fan ◽  
Yanhong Li ◽  
Jie Wang ◽  
Jiahao Shao ◽  
Tao Tang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Muscle Metabolism ◽  
Principal Component ◽  
Oxidative Capacity ◽  
Ultra Performance Liquid Chromatography ◽  
Normal Diet ◽  
High Fat ◽  
Tissue Samples

Type 2 diabetes and metabolic syndrome caused by a high fat diet (HFD) have become public health problems worldwide. These diseases are characterized by the oxidation of skeletal muscle mitochondria and disruption of insulin resistance, but the mechanisms are not well understood. Therefore, this study aims to reveal how high-fat diet causes skeletal muscle metabolic disorders. In total, 16 weaned rabbits were randomly divided into two groups, one group was fed a standard normal diet (SND) and the other group was fed a high fat diet (HFD) for 5 weeks. At the end of the five-week experiment, skeletal muscle tissue samples were taken from each rabbit. Untargeted metabolomic analysis was performed using ultra-performance liquid chromatography combined with mass spectrometry (UHPLC-MS/MS). The results showed that high fat diet significantly altered the expression levels of phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosterone in skeletal muscle. Principal component analysis (PCA) and least squares discriminant analysis (PLS-DA) showed that, compared with the SND group, skeletal muscle metabolism in HFD group was significantly up-regulated. Among 43 skeletal muscle metabolites in the HFD group, phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosteroids were identified as biomarkers of skeletal muscle metabolic diseases, and may become potential physiological targets of related diseases in the future. Untargeted metabonomics analysis showed that high-fat diet altered the metabolism of phospholipids, carnitine, amino acids and steroids in skeletal muscle of rabbits. Notably, phospholipids, LCACs, histidine, carnopeptide, and tetrahydrocorticosteroids block the oxidative capacity of mitochondria and disrupt the oxidative capacity of glucose and the fatty acid-glucose cycle in rabbit skeletal muscle.

scholarly journals Effect of Ethyl Pyruvate on Skeletal Muscle Metabolism in Rats Fed on a High Fat Diet

Nutrients ◽  
2013 ◽  
Vol 5 (7) ◽  
pp. 2372-2383 ◽  
Author(s):  
Robert Olek ◽  
Wieslaw Ziolkowski ◽  
Tomasz Wierzba ◽  
Jan Kaczor
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Ethyl Pyruvate ◽  
Muscle Metabolism ◽  
High Fat ◽  
Skeletal Muscle Metabolism

Increased body fat mass and tissue lipotoxicity associated with ovariectomy or high-fat diet differentially affects bone and skeletal muscle metabolism in rats

2014 ◽  
Vol 54 (7) ◽  
pp. 1139-1149 ◽  
Author(s):  
Camille Tagliaferri ◽  
Jérôme Salles ◽  
Jean-François Landrier ◽  
Christophe Giraudet ◽  
Véronique Patrac ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Fat ◽  
Fat Mass ◽  
High Fat Diet ◽  
Muscle Metabolism ◽  
Body Fat Mass ◽  
High Fat ◽  
Skeletal Muscle Metabolism

scholarly journals Postprandial Skeletal Muscle Metabolism Following a High Fat Diet in Sedentary and Endurance Trained Males

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Mary Elizabeth Baugh ◽  
Suzanne M Bowser ◽  
Ryan P McMillan ◽  
Brenda M Davy ◽  
Matthew W Hulver ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Muscle Metabolism ◽  
High Fat ◽  
Skeletal Muscle Metabolism

Abstract 394: Posttranslational Modification Of Klf5 Mediates Metabolic Dysfunction And Vascular Disease In Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yumiko Oishi ◽  
Ichiro Manabe ◽  
Kazuyuki Tobe ◽  
Takashi Kadowaki ◽  
Ryozo Nagai
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Energy Expenditure ◽  
Posttranslational Modifications ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
C2c12 Myotubes ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Increased Risk

We have previously shown that a zinc finger transcription factor, Krüppel-like factor 5 (KLF5), plays an important role in pathogenesis of cardiovascular diseases, such as atherosclerosis. KLF5 heterozygous knockout ( KLF5 +/ − ) mice exhibited much less neointima formation, cardiac hypertrophy and fibrosis. We also found that expression of KLF5 correlated with a higher incidence of restenosis following PCI and the SNP located within the KLF5 promoter was associated with an increased risk of hypertension in man. Interestingly, KLF5 is also expressed in metabolic tissues such as adipose tissue, skeletal muscle, and pancreatic β-cells. Thus, we hypothesized that KLF5 might play a role in metabolic diseases. To test this, KLF5 +/ − mice were fed with high-fat diet. Although KLF5 +/ − mice ate more food than wild-type littermates, they were resistant to high-fat diet-induced obesity and protected from dyslipidemia, glucose intolerance and hepatic steatosis, indicating that KLF5 + /− mice were less susceptible to metabolic syndrome. The systemic O 2 consumption and expression of genes involved in energy expenditure in skeletal muscle were increased in KLF5 + /− mice, demonstrating enhanced energy expenditure, which partly explains the phenotype. Knocking down KLF5 by siRNA increased expression levels of UCP2/3 and CPT-1b in C2C12 myotubes, suggesting that KLF5 may inhibit energy expenditure-related genes. Chromatin immunoprecipitation and coimmunoprecipitation assays showed that KLF5 interacted with corepressors, such as SMRT and NCoR, and strongly inhibited the UCP and CPT-1b promoters. We found that this inhibitory activity of KLF5 depended on its SUMOylation. When KLF5 was deSUMOylated, it activated the promoters. These data demonstrate that KLF5 acts as a molecular switch for energy expenditure and the posttranslational modifications of KLF5 including SUMOylation turns on/off the switch function of KLF5. Given that KLF5 also controls tissue remodeling in response to external stress, KLF5 may mediate metabolic dysfunction and atherosclerosis in metabolic syndrome. Our findings also suggest that the posttranscriptional modification of KLF5 is an attractive novel therapeutic target.

scholarly journals Monitoring the Transition Period in Dairy Cows through 1H NMR-Based Untargeted Metabolomics

Dairy ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 356-366
Author(s):  
Andrés López Radcenco ◽  
María de Lourdes Adrien ◽  
Gretel Ruprechter ◽  
Elena de Torres ◽  
Ana Meikle ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Milk Production ◽  
1H Nmr ◽  
Metabolic Diseases ◽  
Transition Period ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Untargeted Metabolomics ◽  
The Impact

The metabolic alterations associated with the increase in milk production make the transition period critical to the health of dairy cows, usually leading to a higher incidence of disease in periparturient animals. In this manuscript, we describe the use of NMR-based untargeted metabolomics to follow how these changes impact the serum metabolome in a group of 28 transition dairy cows with no initial clinical diseases. Principal component analysis (PCA) of serum 1H NMR data from four weeks before calving to 8 weeks after parturition allowed us to clearly identify four stages during the transition period. Pairwise comparisons using orthogonal partial least square discriminant analysis (OPLS-DA) and univariate data analysis led to the identification of 18 metabolites that varied significantly through these stages. Species such as acetate, betaine, and creatine are observed early after calving, while other markers of metabolic stress, including acetone, β-hydroxybutyrate (BHB), and choline, accumulate significantly at the height of milk production. Furthermore, marked variations in the levels of lactate, allantoin, alanine, and other amino acids reveal the activation of different gluconeogenic pathways following parturition. Concomitant with a return to homeostasis, a gradual normalization of the serum metabolome occurs 8 weeks after calving. Correlations of metabolite levels with dietary and metabolic adaptations based on animal parity could also be identified. Overall, these results show that NMR-based chemometric methods are ideally suited to monitor manifestations of metabolic diseases throughout the transition period and to assess the impact of nutritional management schemes on the metabolism of dairy cows.

Abstract 17649: Inhibition of Src Homology 2 Domain-containing Phosphatase 1 (SHP-1) Increases Insulin Sensitivity in High-fat Diet-induced Insulin Resistant C57black6 Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Janine Krüger ◽  
Markus Dagnell ◽  
Philipp Stawowy ◽  
Evren Caglayan ◽  
Arne Östman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
High Fat ◽  
Insulin Resistant ◽  
Cardiovascular Morbidity And Mortality

Background: Insulin resistance plays a crucial role in the development of type 2 diabetes, and exerts great impact on vascular inflammation and remodeling. At the molecular level a post-insulin receptor (IR) defect in insulin signaling has been suggested to contribute to insulin resistance. IR signaling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). The precise role of PTPs in insulin resistance, however, has not been explored. Results: Male C57BL/6J mice were fed a high-fat diet (HFD, 60% kcal from fat) to induce insulin resistance, or a low-fat diet (LFD, 10% kcal from fat) for 10 weeks. Afterwards, HFD mice were treated with PTP-inhibitors for additional 6 weeks. Mice under HFD exhibited a significant increase in body weight as well as decreased respiratory quotient and adiponectin levels, and were characterized by impaired insulin- and glucose tolerance. Organ-based gene expression analyses in insulin-resistant mice demonstrated upregulation of SHP-1, PTP1B, LAR, and DEP-1 in insulin-sensitive organs. SHP-1 was further explored in vitro. Insulin stimulation in murine liver cells induced site-selective hyper-phosphorylation at IR tyrosine-sites Y1158, and Y1361 after inhibition of SHP-1. Furthermore, SHP-1 impairment time-dependently enhanced insulin-induced Akt- and Erk-phosphorylation, and resulted in elevated glucose uptake in skeletal muscle cells. Administration of a SHP-1 inhibitor (Sodium Stibogluconate) and a brought pan-PTP inhibitor (BMOV) in HFD mice led to improvement of both insulin- and glucose tolerance. In accordance, PTP-activity was significantly impaired in epididymal fat, skeletal muscle, and liver under BMOV treatment, being confirmed by reduced ex vivo dephosphorylation of a radioactive labelled peptide (AEEEIYGEFEAKKKK). Finally, BMOV- and SHP-1 treatment also resulted in reduced body weight. Conclusions: IR-antagonizing PTPs were organ-specifically regulated in insulin resistance. The results indicate a central role of PTPs and, in particular, of SHP-1 as endogenous antagonists of the IR. Taken together targeting PTPs led to beneficial effects in insulin resistance, and may thus improve metabolic diseases as well as cardiovascular morbidity and mortality.

scholarly journals The Effect of Exercise Training on Myocardial and Skeletal Muscle Metabolism by MR Spectroscopy in Rats with Heart Failure

Metabolites ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 53 ◽  
Author(s):  
Mingshu Shi ◽  
Øyvind Ellingsen ◽  
Tone Bathen ◽  
Morten Høydal ◽  
Tomas Stølen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Training Session ◽  
Muscle Metabolism ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Metabolic Profiles ◽  
Skeletal Muscle Metabolism

The metabolism and performance of myocardial and skeletal muscle are impaired in heart failure (HF) patients. Exercise training improves the performance and benefits the quality of life in HF patients. The purpose of the present study was to determine the metabolic profiles in myocardial and skeletal muscle in HF and exercise training using MRS, and thus to identify targets for clinical MRS in vivo. After surgically establishing HF in rats, we randomized the rats to exercise training programs of different intensities. After the final training session, rats were sacrificed and tissues from the myocardial and skeletal muscle were extracted. Magnetic resonance spectra were acquired from these extracts, and principal component and metabolic enrichment analysis were used to assess the differences in metabolic profiles. The results indicated that HF affected myocardial metabolism by changing multiple metabolites, whereas it had a limited effect on skeletal muscle metabolism. Moreover, exercise training mainly altered the metabolite distribution in skeletal muscle, indicating regulation of metabolic pathways of taurine and hypotaurine metabolism and carnitine synthesis.

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