miRNA-22 deletion limits white adipose expansion and activates brown fat to attenuate high-fat diet-induced fat mass accumulation

Lima, Vanessa Batista de Sousa; Liu, Jianming; Brandão, Bruna B.; Lino, Caroline Antunes; Silva, Camila S Balbino; Ribeiro, Márcio Augusto Campos; Oliveira, Tiago E.; Real, Caroline Cristiano; Faria, Daniele de Paula; Cederquist, Carly; Huang, Zhan-Peng; Hu, Xiaoyun; Barreto‐Chaves, Maria Luíza Morais; Ferreira, Julio Cesar Batista; Festuccia, William T.; Mori, Marcelo A.; Kahn, C. Ronald; Wang, Dazhi; Diniz, Gabriela Placoná

doi:10.1016/j.metabol.2021.154723

Cited by 22 publications

(11 citation statements)

References 62 publications

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“…White adipocyte cultures were prepared as previously described [35]. The 3T3-L1 cells were differentiated into white adipocytes in medium containing 1 mM dexamethasone, 0.125 mM indomethacin, 1 mM insulin, and 0.5 mM isobutylmethylxanthine for 7 days.…”

Section: White Adipocyte Culturementioning

confidence: 99%

Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice

Miranda

Lunardon

Lima

et al. 2022

Cell Physiol Biochem

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Background/Aims: An obesogenic diet (high fat and sugar, low fiber) is associated with an increased risk for metabolic and cardiovascular disorders. Previous studies have demonstrated that epigenetic changes can modify gene transcription and protein function, playing a key role in the development of several diseases. The methyltransferase Set7 methylates histone and non-histone proteins, influencing diverse biological and pathological processes. However, the functional role of Set7 in obesity-associated metabolic and cardiovascular complications is unknown. Methods: Wild type and Set7 knockout female mice were fed a normal diet or an obesogenic diet for 12 weeks. Body weight gain and glucose tolerance were measured. The 3T3-L1 cells were used to determine the role of Set7 in white adipogenic differentiation. Cardiac morphology and function were evaluated by histology and echocardiography. An ex vivo Langendorff perfusion system was used to model cardiac ischemia/reperfusion (I/R). Results: Here, we report that Set7 protein levels were enhanced in the heart and perigonadal adipose tissue (PAT) of female mice fed an obesogenic diet. Significantly, loss of Set7 prevented obesogenic diet-induced glucose intolerance in female mice although it did not affect the obesogenic diet-induced increase in body weight gain and adiposity in these animals, nor did Set7 inhibition change white adipogenic differentiation in vitro. In addition, loss of Set7 prevented the compromised cardiac functional recovery following ischemia and reperfusion (I/R) injury in obesogenic diet-fed female mice; however, deletion of Set7 did not influence obesogenic diet-induced cardiac hypertrophy nor the hemodynamic and echocardiographic parameters. Conclusion: These data indicate that Set7 plays a key role in obesogenic diet-induced glucose intolerance and compromised myocardial functional recovery after I/R in obese female mice.

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Section: White Adipocyte Culturementioning

confidence: 99%

Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice

Miranda

Lunardon

Lima

et al. 2022

Cell Physiol Biochem

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“…In diet-induced obese mice, circulating levels of miR-22, miR-122 and miR-192 in sEVs are increased, but after 8 weeks of aerobic exercise, return to levels similar to lean controls (de Mendonca et al 2020). miR-22 is known to regulate adipose tissue expansion (its genetic ablation reduces adipose tissue mass) and activate thermogenesis (Lima et al 2021). miR-122 is increased in adipose tissue, liver and the circulation of subjects with fatty liver disease, obesity and T2D (Willeit et al 2017), and miR-192 is increased in the circulation of prediabetic patients (Parrizas et al 2015).…”

Section: Effect Of Weight Loss Intervention On Obesity-associated Mirnasmentioning

confidence: 99%

“…miR‐22 is known to regulate adipose tissue expansion (its genetic ablation reduces adipose tissue mass) and activate thermogenesis (Lima et al . 2021). miR‐122 is increased in adipose tissue, liver and the circulation of subjects with fatty liver disease, obesity and T2D (Willeit et al .…”

Section: Introductionmentioning

confidence: 99%

Extracellular miRNAs as mediators of obesity‐associated disease

Brandão

Lino

Kahn

2021

The Journal of Physiology

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Extracellular miRNAs are found in a variety of body fluids and mediate intercellular and interorgan communication, thus regulating gene expression and cellular metabolism. These miRNAs are secreted either in small vesicles/exosomes (sEV) or bound to proteins such as Argonaute and high-density lipoprotein. Both exosomal and protein-bound circulating miRNAs are altered in obesity. Although all tissues can contribute to changes in circulating miRNAs, adipose tissue itself is an important source of these miRNAs, especially those in sEVs. These are derived from both adipocytes and macrophages and participate in crosstalk between these cells, as well as peripheral tissues, including liver, skeletal muscle and pancreas, whose function may be impaired in obesity. Changes in levels of circulating miRNAs have also been linked to the beneficial effects induced by weight loss interventions, including diet, exercise and bariatric surgery, further indicating a role for these miRNAs as mediators of disease pathogenesis. Here, we review the role of circulating miRNAs in the pathophysiology of obesity and explore their potential use as biomarkers and in therapy of obesity-associated metabolic syndrome.

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“…hsa-miR-22-3p is an example of another miRNA that is involved in the regulation of the proinflammatory response, whose expression correlated negatively with ESR1 mRNA levels in the SAT of obese participants in our study. Since deletion of this miRNA attenuates the accumulation of adipose tissue by reducing white adipocyte differentiation in animal models, its increased concentrations in human SAT during obesity may not only neutralize the beneficial effects of ESR1 activation but also promote excess fat accumulation [ 27 , 51 ]. hsa-miR-100-5p and hsa-miR-143-5p are the two molecules that regulate the response to therapy in ER-positive breast cancers [ 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Estrogen Receptor Genes’ Expressions in Adipose Tissue in the Course of Obesity

Koźniewski

Wąsowski

Jonas

et al. 2022

IJMS

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Estrogen affects adipose tissue function. Therefore, this study aimed at assessing changes in the transcriptional activity of estrogen receptor (ER) α and β genes (ESR1 and ESR2, respectively) in the adipose tissues of obese individuals before and after weight loss and verifying whether epigenetic mechanisms were involved in this phenomenon. ESR1 and ESR2 mRNA and miRNA levels were evaluated using real-time PCR in visceral (VAT) and subcutaneous adipose tissue (SAT) of 78 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI = 20–24.9 kg/m2) individuals and in 19 SAT samples from post-bariatric patients. ESR1 and ESR2 methylation status was studied using the methylation-sensitive digestion/real-time PCR method. Obesity was associated with a decrease in mRNA levels of both ERs in SAT (p < 0.0001) and ESR2 in VAT (p = 0.0001), while weight loss increased ESR transcription (p < 0.0001). Methylation levels of ESR1 and ESR2 promoters were unaffected. However, ESR1 mRNA in the AT of obese subjects correlated negatively with the expression of hsa-miR-18a-5p (rs = −0.444), hsa-miR-18b-5p (rs = −0.329), hsa-miR-22-3p (rs = −0.413), hsa-miR-100-5p (rs = −0.371), and hsa-miR-143-5p (rs = −0.289), while the expression of ESR2 in VAT correlated negatively with hsa-miR-576-5p (rs=-0.353) and in SAT with hsa-miR-495-3p (rs = −0.308). In conclusion, obesity-associated downregulation of ER mRNA levels in adipose tissue may result from miRNA interference.

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miRNA-22 deletion limits white adipose expansion and activates brown fat to attenuate high-fat diet-induced fat mass accumulation

Cited by 22 publications

References 62 publications

Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice

Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function After Ischemia and Reperfusion in Obese Female Mice

Extracellular miRNAs as mediators of obesity‐associated disease

Epigenetic Regulation of Estrogen Receptor Genes’ Expressions in Adipose Tissue in the Course of Obesity

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