MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice

Mendonça, Mariana de; Sousa, Eduinetty Ceci Pereira Moreira de; Paixão, Ailma Oliveira da; Santos, Bruna Araújo dos; Spagnol, Alexandre Roveratti; Murata, Gilson Masahiro; Araújo, Hygor N.; Lima, Tanes I.; Guimarães, Dimitrius Santiago Passos Simões Fróes; Silveira, Leonardo R.; Rodrigues, Alice Cristina

doi:10.1016/j.mce.2019.110661

Cited by 12 publications

(13 citation statements)

References 55 publications

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“…In a previous study, miR‐222‐3p was found to be increased in skeletal muscle, plasma, and plasma EVs after exercise 37 . miR‐222‐3p may regulate myoblast proliferation and myofiber formation 42,43 or insulin sensitivity in cultured muscle cells 44 . Interestingly, also miR‐30a‐5p and miR‐10b‐5p have been implicated in the regulation of muscle cell proliferation and/or differentiation 45,46 .…”

Section: Discussionmentioning

confidence: 93%

Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight

et al. 2022

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Extracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear. Aim:The aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long-term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors.Methods: Sedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12-week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography.Results: Extracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR-652-3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR-32-5p and miR-339-3p, that were strongly correlated to an adipose tissue macrophage signature. Conclusion:Numerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise-induced extracellular vesicles and cargo miRNA to clarify where exercise-induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.

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Section: Discussionmentioning

confidence: 93%

Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight

et al. 2022

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“…The importance of Mir222 in the pathogenesis of obesity is supported by the analysis of adipose tissue-specific Dicer knockout mice, in which gonadal adipose tissue was the main source of serum exosomal miR-222 ( 19 ). The exosome-packed Mir222 influenced remote organs, and overexpression of Mir222 inhibits the expression of IRS-1 by directly binding to untranslated regions in the muscle ( 20 ) and liver ( 21 ). In current investigation, we firstly demonstrated that overexpression of Mir222 promoted the adipogenesis in 3T3-L1 cells.…”

Section: Discussionmentioning

confidence: 99%

Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4

et al. 2022

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MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222flox/y. Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy.

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“…The two mouse SO muscles were isolated, attached to stainless steel clips to maintain resting tension, and preincubated with Krebs-Ringer bicarbonate buffer containing glucose in the presence or absence of insulin 7 nM, as previously described ( de Mendonça et al, 2020a ). The muscles were briefly washed in cold KRBB at 4°C, dried on filter paper, and frozen in liquid N2.…”

Section: Methodsmentioning

confidence: 99%

Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice

et al. 2021

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The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

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MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice

Cited by 12 publications

References 55 publications

Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight

Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight

Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4

Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice

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