Transcriptome and proteomics analysis revealed key genes in rabbit skeletal muscle after weight loss

Abstract Skeletal muscle is one of the important organs of energy metabolism and is closely related to insulin secretion. Its metabolic characteristics have a major influence on fat distribution in various body tissues. However, rabbit skeletal muscle has lower intramuscular fat content, and its metabolic mechanism is still unclear. We investigated skeletal muscle growth and metabolic differences among rabbits using a comparative multi-omics approach after a 14-day weight loss by a restricted diet. Rabbit body weight and perirenal fat were significantly reduced after the weight loss. Transcriptomics data revealed 917 differentially expressed genes in skeletal muscle primarily enriched in the FOXO signaling, Glutathione metabolism, and AMPK signaling pathways. Proteomics data found 127 differential proteins concentrated in protein metabolism and immunoinflammatory pathways. Conbined analysis demonstrated that eight genes (ATP2A2, PDLIM3, GPX7, FKBP5, MYL3, COL5A2, UCHL1, and COL3A1) were strongly correlated at the transcriptional and translational levels. These results provide a good reference for further revealing the mechanism of skeletal muscle metabolism in rabbits.

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Dynamic changes of muscle insulin sensitivity after metabolic surgery

Nature Communications ◽

10.1038/s41467-019-12081-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Sofiya Gancheva ◽

Meriem Ouni ◽

Tomas Jelenik ◽

Chrysi Koliaki ◽

Julia Szendroedi ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Metabolic Surgery ◽

Muscle Metabolism ◽

Respiratory Control ◽

Oxidative Capacity ◽

Initial Weight Loss ◽

Expression Of Genes

Abstract The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity.

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Increased fat mass, decreased myofiber size, and a shift to glycolytic muscle metabolism in adolescent male transgenic mice overexpressing IGFBP-2

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00492.2009 ◽

2010 ◽

Vol 299 (2) ◽

pp. E287-E298 ◽

Cited By ~ 27

Author(s):

Charlotte Rehfeldt ◽

Ulla Renne ◽

Mandy Sawitzky ◽

Gerhard Binder ◽

Andreas Hoeflich

Keyword(s):

Skeletal Muscle ◽

Transgenic Mice ◽

Muscle Growth ◽

Muscle Metabolism ◽

Adolescent Male ◽

Signal Molecules ◽

Fat Percentage ◽

Ki 67 ◽

Phosphorylated Akt

To elucidate the functional role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) for in vivo skeletal muscle growth and function, skeletal muscle cellularity and metabolism, expression of signal molecules, and body growth and composition were studied in a transgenic mouse model overexpressing IGFBP-2. Postnatal growth rate of transgenic mice was reduced from day 21 of age by 6–8% compared with nontransgenic controls. At 10 wk of age body lean protein and moisture percentages were lower, whereas fat percentage was higher in IGFBP-2 transgenic mice. Muscle weights were reduced (−13% on day 30 of age, −14% on day 72), which resulted from slower growth of myofibers in size but not from decreases in myofiber number. The reduction in muscle mass was associated with lower total DNA, RNA, and protein contents as well as greater DNA/RNA and protein/RNA ratios. The percentage of proliferating (Ki-67-positive) nuclei within myofibers was reduced (3.4 vs. 5.8%) in 30-day-old transgenic mice. These changes were accompanied by slight reductions in specific p44/42 MAPK activity (−18% on day 72) and, surprisingly, by increased levels of phosphorylated Akt (Ser473) (+25% on day 30, +66% on day 72). The proportion of white glycolytic fibers (55.9 vs. 53.5%) and the activity of lactate dehydrogenase (+8%) were elevated in 72-day-old transgenic mice. Most of the differences observed between transgenic and nontransgenic mice were more pronounced in males. The results suggest that IGFBP-2 significantly inhibits postnatal skeletal myofiber growth by decreasing myogenic proliferation and protein accretion and enhances glycolytic muscle metabolism.

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Circadian clock regulation of skeletal muscle growth and repair

F1000Research ◽

10.12688/f1000research.9076.1 ◽

2016 ◽

Vol 5 ◽

pp. 1549 ◽

Cited By ~ 22

Author(s):

Somik Chatterjee ◽

Ke Ma

Keyword(s):

Skeletal Muscle ◽

Circadian Clock ◽

Muscle Growth ◽

Muscle Metabolism ◽

Muscle Physiology ◽

Skeletal Muscle Growth ◽

Age Related ◽

Evolutionarily Conserved ◽

Key Aspects ◽

And Function

Accumulating evidence indicates that the circadian clock, a transcriptional/translational feedback circuit that generates ~24-hour oscillations in behavior and physiology, is a key temporal regulatory mechanism involved in many important aspects of muscle physiology. Given the clock as an evolutionarily-conserved time-keeping mechanism that synchronizes internal physiology to environmental cues, locomotor activities initiated by skeletal muscle enable entrainment to the light-dark cycles on earth, thus ensuring organismal survival and fitness. Despite the current understanding of the role of molecular clock in preventing age-related sarcopenia, investigations into the underlying molecular pathways that transmit clock signals to the maintenance of skeletal muscle growth and function are only emerging. In the current review, the importance of the muscle clock in maintaining muscle mass during development, repair and aging, together with its contribution to muscle metabolism, will be discussed. Based on our current understandings of how tissue-intrinsic muscle clock functions in the key aspects muscle physiology, interventions targeting the myogenic-modulatory activities of the clock circuit may offer new avenues for prevention and treatment of muscular diseases. Studies of mechanisms underlying circadian clock function and regulation in skeletal muscle warrant continued efforts.

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

10.21203/rs.3.rs-159084/v1 ◽

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.

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Multi–Omics Analysis of Key microRNA–mRNA Metabolic Regulatory Networks in Skeletal Muscle of Obese Rabbits

International Journal of Molecular Sciences ◽

10.3390/ijms22084204 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4204

Author(s):

Yanhong Li ◽

Jie Wang ◽

Mauricio A. Elzo ◽

Mingchuan Gan ◽

Tao Tang ◽

...

Keyword(s):

Skeletal Muscle ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Metabolic Diseases ◽

Muscle Metabolism ◽

Rabbit Skeletal Muscle ◽

Differentially Expressed ◽

Control Group ◽

Small Rna Sequencing ◽

Non Coding Rna

microRNAs (miRNAs), small non-coding RNA with a length of about 22 nucleotides, are involved in the energy metabolism of skeletal muscle cells. However, their molecular mechanism of metabolism in rabbit skeletal muscle is still unclear. In this study, 16 rabbits, 8 in the control group (CON–G) and 8 in the experimental group (HFD–G), were chosen to construct an obese model induced by a high–fat diet fed from 35 to 70 days of age. Subsequently, 54 differentially expressed miRNAs, 248 differentially expressed mRNAs, and 108 differentially expressed proteins related to the metabolism of skeletal muscle were detected and analyzed with three sequencing techniques (small RNA sequencing, transcriptome sequencing, and tandem mass tab (TMT) protein technology). It was found that 12 miRNAs and 12 core genes (e.g., CRYL1, VDAC3 and APIP) were significantly different in skeletal muscle from rabbits in the two groups. The network analysis showed that seven miRNA-mRNA pairs were involved in metabolism. Importantly, two miRNAs (miR-92a-3p and miR-30a/c/d-5p) regulated three transcription factors (MYBL2, STAT1 and IKZF1) that may be essential for lipid metabolism. These results enhance our understanding of molecular mechanisms associated with rabbit skeletal muscle metabolism and provide a basis for future studies in the metabolic diseases of human obesity.

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