The Potential Role of Contraction-Induced Myokines in the Regulation of Metabolic Function for the Prevention and Treatment of Type 2 Diabetes

Carson, Brian P.

doi:10.3389/fendo.2017.00097

Cited by 63 publications

(47 citation statements)

References 79 publications

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“…Adipose tissue not only cushions and insulates the body and stores energy in the form of lipids but also secretes adipokines that regulate systemic processes such as food intake and nutrient metabolism, insulin sensitivity, glucose homeostasis, cell proliferation, inflammation, and angiogenesis 3 , 4 . Skeletal muscle is associated with insulin-dependent glucose metabolism, and its contraction produces myokine control adaptive processes in skeletal muscle by regulating fuel oxidation, hypertrophy, angiogenesis, and inflammatory processes 1 , 5 . Both adipose- and skeletal muscle-derived adipokines and myokines have detrimental or beneficial effects in the prevention and treatment of metabolic diseases such as obesity and type II diabetes 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

He¹,

Li²,

Tang³

et al. 2018

Int. J. Biol. Sci.

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The recently developed high-throughput chromatin conformation capture (Hi-C) technology enables us to explore the spatial architecture of genomes, which is increasingly considered an important regulator of gene expression. To investigate the changes in three-dimensional (3D) chromatin structure and its mediated gene expression during adipogenesis and myogenesis, we comprehensively mapped 3D chromatin organization for four cell types (3T3-L1 pre-adipocytes, 3T3-L1-D adipocytes, C2C12 myoblasts, and C2C12-D myotubes). We demonstrate that the dynamic spatial genome architecture affected gene expression during cell differentiation. A considerable proportion (~22%) of the mouse genome underwent compartment A/B rearrangement during adipogenic and myogenic differentiation, and most (~80%) upregulated marker genes exhibited an active chromatin state with B to A switch or stable A compartment. More than half (65.4%-73.2%) of the topologically associating domains (TADs) are dynamic. The newly formed TAD and intensified local interactions in the Fabp gene cluster indicated more precise structural regulation of the expression of pro-differentiation genes during adipogenesis. About half (32.39%-59.04%) of the differential chromatin interactions (DCIs) during differentiation are promoter interactions, although these DCIs only account for a small proportion of genome-wide interactions (~9.67% in adipogenesis and ~4.24% in myogenesis). These differential promoter interactions were enriched with promoter-enhancer interactions (PEIs), which were mediated by typical adipogenic and myogenic transcription factors. Differential promoter interactions also included more differentially expressed genes than nonpromoter interactions. Our results provide a global view of dynamic chromatin interactions during adipogenesis and myogenesis and are a resource for studying long-range chromatin interactions mediating the expression of pro-differentiation genes.

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Section: Introductionmentioning

confidence: 99%

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

He¹,

Li²,

Tang³

et al. 2018

Int. J. Biol. Sci.

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“…We next examined the potential roles of myokines as important mediators of skeletal muscle fiber growth, hypertrophy, glucose uptake, and fiber type distribution in muscles . The protein levels of IL‐6, IL‐15, fibronectin type III domain containing 5 (FNDC5), and myostatin were higher in OLETF‐C rats than in age‐matched LETO‐C rats ( P < 0.05; Figure A‐C).…”

Section: Resultsmentioning

confidence: 99%

Long‐term insulin treatment leads to a change in myosin heavy chain fiber distribution in OLETF rat skeletal muscle

Hong

Choi

Kwon

et al. 2018

J of Cellular Biochemistry

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The objective of this study was to investigate molecular and physiological changes in response to long-term insulin glargine treatment in the skeletal muscle of OLETF rats. Male Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats aged 24 weeks were randomly allocated to either treatment with insulin for 24 weeks or no treatment, resulting in three groups. Insulin glargine treatment in OLETF rats (OLETF-G) for 24 weeks resulted in changes in blood glucose levels in intraperitoneal glucose tolerance tests compared with age-matched, untreated OLETF rats (OLETF-C), and the area under the curve was significantly decreased for OLETF-G rats compared with OLETF-C rats (P < 0.05). The protein levels of MHC isoforms were altered in gastrocnemius muscle of OLETF rats, and the proportions of myosin heavy chain type I and II fibers were lower and higher, respectively, in OLETF-G compared with OLETF-C rats. Activation of myokines (IL-6, IL-15, FNDC5, and myostatin) in gastrocnemius muscle was significantly inhibited in OLETF-G compared with OLETF-C rats ( P < 0.05). MyoD and myogenin levels were decreased, while IGF-I and GLUT4 levels were increased, in the skeletal muscle of OLETF-G rats ( P < 0.05). Insulin glargine treatment significantly increased the phosphorylation levels of AMPK, SIRT1, and PGC-1α. Together, our results suggested that changes in the distribution of fiber types by insulin glargine could result in downregulation of myokines and muscle regulatory proteins. The effects were likely associated with activation of the AMPK/SIRT1/PGC-1α signaling pathway. Changes in these proteins may at least partly explain the effect of insulin in skeletal muscle of diabetes mellitus.

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“…Exercise‐induced myokines are recognized as central players in both the prevention and treatment of type 2 diabetes. To date, several hundred myokines in the muscle secretome have been identified, a subpopulation of which are specifically induced by skeletal muscle contractions [32]. However, the bioactivity of many of these myokines and the mechanisms through which they act have either not yet been characterized or remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

The myokine meteorin‐like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2

et al. 2020

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Meteorin-like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium-dependent AMPKa2 pathway in skeletal muscle cells and increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPKa2dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. An intraperitoneal injection of recombinant metrnl improved glucose tolerance in mice with high-fat-diet-induced obesity or type 2 diabetes, but not in AMPK b1b2 muscle-specific null mice. Metrnl improves glucose metabolism via AMPKa2 and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.Abbreviations ACC, acetyl-CoA carboxylase; AMPK, AMP-activated protein kinase; BAPTA-AM, 1,2-Bis (2-aminophenoxy) ethane-N,N,N 0 ,N 0 -tetraacetic acid tetrakis (acetoxymethyl ester; EPS, electrical pulse stimulation; GLUT4, glucose transporter type 4; GST, glutathione S-transferase; GTT, glucose tolerance test; HDAC5, histone deacetylase 5; HFD, high-fat diet; ICC, immunocytochemistry; MAPK, mitogen-activated protein kinase; TBC1D1, TBC1 domain family member 1.

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The Potential Role of Contraction-Induced Myokines in the Regulation of Metabolic Function for the Prevention and Treatment of Type 2 Diabetes

Cited by 63 publications

References 79 publications

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

Long‐term insulin treatment leads to a change in myosin heavy chain fiber distribution in OLETF rat skeletal muscle

The myokine meteorin‐like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2

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