Muscle miR-16 deletion results in impaired insulin sensitivity and contractile function in a sex-dependent manner

Lim, Seongkyun; Deaver, J. William; Rosa‐Caldwell, Megan E.; Lee, David E.; Silva, Francielly Morena da; Cabrera, Ana Regina; Schrems, Eleanor R.; Saling, Landen W.; Washington, Tyrone A.; Fluckey, James D.

doi:10.1152/ajpendo.00333.2021

Cited by 9 publications

(5 citation statements)

References 56 publications

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“…Circulating miR-16 was increased in GDM samples ( Figure 5 A) and was reported, together with miR-29a and miR-134, to form a predictive biomarker algorithm for GDM [ 21 ]. Interestingly, deletion of miR-16-5p in skeletal muscle positively correlates with insulin sensitivity [ 79 ], and circulating levels of miR-16-5p are also correlated positively with insulin sensitivity [ 80 ], which is not well-reconciled with circulating miR-16-5p being increased in GDM, which is a state characterized by impaired insulin sensitivity. However, Cao et al (2017) [ 30 ] found circulating miR-16-5p levels to be highly correlated with insulin resistance, measured with the HOMA-IR index.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

Dinesen

El-Faitarouni

Frisk

et al. 2023

IJMS

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Gestational diabetes mellitus (GDM) is a severe pregnancy complication for both the woman and the child. Women who suffer from GDM have a greater risk of developing Type 2 diabetes mellitus (T2DM) later in life. Identification of any potential biomarkers for the early prediction of gestational diabetes can help prevent the disease in women with a high risk. Studies show microRNA (miRNA) as a potential biomarker for the early discovery of GDM, but there is a lack of clarity as to which miRNAs are consistently altered in GDM. This study aimed to perform a systematic review and meta-analysis to investigate miRNAs associated with GDM by comparing GDM cases with normoglycemic controls. The systematic review was performed according to PRISMA guidelines with searches in PubMed, Web of Science, and ScienceDirect. The primary search resulted in a total of 849 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 35 full-text articles, which were evaluated for risk of bias and estimates of quality, after which data were extracted and relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: MiR-29a, miR-330, miR-134, miR-132, miR-16, miR-223, miR-155, miR-122, miR-17, miR-103, miR-125, miR-210, and miR-222. While some miRNAs showed considerable between-study variability, miR-29a, miR-330, miR-134, miR-16, miR-223, and miR-17 showed significant overall upregulation in GDM, while circulating levels of miR-132 and miR-155 were decreased among GDM patients, suggesting further studies of these as biomarkers for early GDM discovery.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

Dinesen

El-Faitarouni

Frisk

et al. 2023

IJMS

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“…Western blots were carried out as previously described (Lim et al., 2022). Briefly, 20 mg of frozen quadriceps and heart muscle samples were powdered and homogenized in Laemmli buffer.…”

Section: Methodsmentioning

confidence: 99%

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

Jones

Dimet²,

Haghani

et al. 2023

The Journal of Physiology

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Exercise promotes functional improvements in aged tissues, but the extent to which it simulates partial molecular reprogramming is unknown. Using transcriptome profiling from (1) a skeletal muscle‐specific in vivo Oct3/4, Klf4, Sox2 and Myc (OKSM) reprogramming‐factor expression murine model; (2) an in vivo inducible muscle‐specific Myc induction murine model; (3) a translatable high‐volume hypertrophic exercise training approach in aged mice; and (4) human exercise muscle biopsies, we collectively defined exercise‐induced genes that are common to partial reprogramming. Late‐life exercise training lowered murine DNA methylation age according to several contemporary muscle‐specific clocks. A comparison of the murine soleus transcriptome after late‐life exercise training to the soleus transcriptome after OKSM induction revealed an overlapping signature that included higher JunB and Sun1. Also, within this signature, downregulation of specific mitochondrial and muscle‐enriched genes was conserved in skeletal muscle of long‐term exercise‐trained humans; among these was muscle‐specific Abra/Stars. Myc is the OKSM factor most induced by exercise in muscle and was elevated following exercise training in aged mice. A pulse of MYC rewired the global soleus muscle methylome, and the transcriptome after a MYC pulse partially recapitulated OKSM induction. A common signature also emerged in the murine MYC‐controlled and exercise adaptation transcriptomes, including lower muscle‐specific Melusin and reactive oxygen species‐associated Romo1. With Myc, OKSM and exercise training in mice, as well habitual exercise in humans, the complex I accessory subunit Ndufb11 was lower; low Ndufb11 is linked to longevity in rodents. Collectively, exercise shares similarities with genetic in vivo partial reprogramming. Key points Advances in the last decade related to cellular epigenetic reprogramming (e.g. DNA methylome remodelling) toward a pluripotent state via the Yamanaka transcription factors Oct3/4, Klf4, Sox2 and Myc (OKSM) provide a window into potential mechanisms for combatting the deleterious effects of cellular ageing. Using global gene expression analysis, we compared the effects of in vivo OKSM‐mediated partial reprogramming in skeletal muscle fibres of mice to the effects of late‐life murine exercise training in muscle. Myc is the Yamanaka factor most induced by exercise in skeletal muscle, and so we compared the MYC‐controlled transcriptome in muscle to Yamanaka factor‐mediated and exercise adaptation mRNA landscapes in mice and humans. A single pulse of MYC is sufficient to remodel the muscle methylome. We identify partial reprogramming‐associated genes that are innately altered by exercise training and conserved in humans, and propose that MYC contributes to some of these responses.

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“…Functional research on miR-16 has mainly focused on diseases [ 33 , 34 , 35 , 36 ]. Muscle miR-16 deletion results in impaired insulin sensitivity and contractile function in a sex-dependent manner [ 37 ]. miR-16-5p suppression protects human cardiomyocytes against endoplasmic reticulum and oxidative stress-induced injury [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

CircRNA Profiling of Skeletal Muscle in Two Pig Breeds Reveals CircIGF1R Regulates Myoblast Differentiation via miR-16

Zhang

et al. 2023

IJMS

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Muscle development is closely related to meat quality and production. CircRNAs, with a closed-ring structure, have been identified as a key regulator of muscle development. However, the roles and mechanisms of circRNAs in myogenesis are largely unknown. Hence, in order to unravel the functions of circRNAs in myogenesis, the present study explored circRNA profiling in skeletal muscle between Mashen and Large White pigs. The results showed that a total of 362 circRNAs, which included circIGF1R, were differentially expressed between the two pig breeds. Functional assays showed that circIGF1R promoted myoblast differentiation of porcine skeletal muscle satellite cells (SMSCs), while it had no effect on cell proliferation. In consideration of circRNA acting as a miRNA sponge, dual-luciferase reporter and RIP assays were performed and the results showed that circIGF1R could bind miR-16. Furthermore, the rescue experiments showed that circIGF1R could counteract the inhibitory effect of miR-16 on cell myoblast differentiation. Thus, circIGF1R may regulate myogenesis by acting as a miR-16 sponge. In conclusion, this study successfully screened candidate circRNAs involved in the regulation of porcine myogenesis and demonstrated that circIGF1R promotes myoblast differentiation via miR-16, which lays a theoretical foundation for understanding the role and mechanism of circRNAs in regulating porcine myoblast differentiation.

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Muscle miR-16 deletion results in impaired insulin sensitivity and contractile function in a sex-dependent manner

Cited by 9 publications

References 56 publications

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

CircRNA Profiling of Skeletal Muscle in Two Pig Breeds Reveals CircIGF1R Regulates Myoblast Differentiation via miR-16

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