Does microRNA Perturbation Control the Mechanisms Linking Obesity and Diabetes? Implications for Cardiovascular Risk

Sala, Lucia La; Crestani, Maurizio; Garavelli, S.; Candia, Paola de; Pontiroli, Antonio E.

doi:10.3390/ijms22010143

Cited by 17 publications

(13 citation statements)

References 141 publications

(153 reference statements)

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“…Recently, obesity‐induced miRNAs have emerged as key regulators of abnormal glucose and lipid metabolism 13 , 14 . In this study, we first demonstrated a novel glucose and lipid metabolism‐associated miRNA, miR‐4431.…”

Section: Discussionmentioning

confidence: 99%

miR‐4431 targets TRIP10/PRKD1 and impairs glucose metabolism

Pan

Wang

et al. 2021

J of Diabetes Invest

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Aim/Introduction Obesity is considered an important risk factor for many metabolic disorders, especially type 2 diabetes mellitus, and microRNAs (miRNAs) play a vital role in the development of type 2 diabetes mellitus. Therefore, we conducted this study to investigate the role of miR‐4431 in the obesity‐associated pathobiology of type 2 diabetes mellitus. Materials and methods Subjects were divided into normal control (n = 36), obese (n = 36), and type 2 diabetes mellitus (n = 12) groups, and serum miR‐4431 levels were analyzed. Adenovirus‐vectored miR‐4431 mimic or sponge was intraperitoneally injected into the normal diet group and the high‐fat diet group (HFD) mice to investigate glucose tolerance, insulin sensitivity, and lipid levels. The downstream target genes of miR‐4431 were predicted using bioinformatics, and they were verified in vitro. Results Serum miR‐4431 levels were significantly high in obese and type 2 diabetes mellitus individuals, and positively correlated with the body mass index and fasting plasma glucose levels. In HFD mice, miR‐4431 levels in the serum, white adipose tissue, and liver were significantly increased. Moreover, miR‐4431 impaired glucose tolerance, insulin sensitivity, and lipid metabolism in mice. Bioinformatic prediction suggested that TRIP10 and PRKD1 could be the downstream target genes of miR‐4431. The HFD mice showed a remarkable reduction in the mRNA levels of TRIP10 and PRKD1 in the liver, which were countered by blocking miR‐4431. In HepG2 and L02 cells, miR‐4431 could downregulate TRIP10 and PRKD1 while blocking glucose uptake. The luciferase reporter assay showed that miR‐4431 could bind TRIP10 and PRKD1 3′‐UTR. Conclusion miR‐4431 targets TRIP10/PRKD1 and impairs glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

miR‐4431 targets TRIP10/PRKD1 and impairs glucose metabolism

Pan

Wang

et al. 2021

J of Diabetes Invest

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“…Furthermore, dysfunctional adipose tissue can partially account for the alterations of RAAS signaling influencing the surrounding organs, including the vasculature. It is well known the paracrine communication between adipose tissue and skeletal muscle, pancreas and cardiovascular system with the release of adipokines, cytokines and other small molecules, such as extracellular vesicles (EV) deputed to vehicle small RNAs (microRNAs) among others [ 44 ]. For example, miR-27a, which plays a critical for obesity by regulating insulin resistance in adipocytes, seems to facilitate the crosstalk between adipocytes and skeletal muscle, inducing insulin resistance by PPARG [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

High plasma renin activity associates with obesity-related diabetes and arterial hypertension, and predicts persistent hypertension after bariatric surgery

Sala

Tagliabue

Vieira

et al. 2021

Cardiovasc Diabetol

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Background Information about the renin–angiotensin–aldosterone system (RAAS) in obese individuals before and after bariatric surgery is scarce. Aim of this study was to analyze the RAAS in severely obese subjects, in relation to anthropometric and metabolic variables, with special reference to glucose tolerance. Methods 239 subjects were evaluated at baseline, and 181 one year after bariatric surgery [laparoscopic gastric banding (LAGB)]. Results At baseline, renin (plasma renin activity, PRA) was increased from normal to glucose tolerance and more in diabetes, also correlating with ferritin. After LAGB, the decrease of PRA and aldosterone was significant in hypertensive, but not in normotensive subjects, and correlatied with decrease of ferritin. PRA and glucose levels were predictive of persistent hypertension 1 year after LAGB. Conclusions These data support the role of RAAS in the pathophysiology of glucose homeostasis, and in the regulation of blood pressure in obesity. Ferritin, as a proxy of subclinical inflammation, could be another factor contributing to the cross-talk between RAAS and glucose metabolism.

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“…MicroRNAs (miRNAs) are a very important part of non-coding RNAs (ncRNAs) and are closely associated with key regulators of metabolic abnormalities [ 87 ]. miRNAs are short noncoding RNA sequences of 18 to 25 nucleotides in length that can regulate gene expression and silence [ 88 ].…”

Section: Mirna-mediated Regulationmentioning

confidence: 99%

Recent progress in epigenetics of obesity

Yin

2022

Diabetol Metab Syndr

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Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.

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Does microRNA Perturbation Control the Mechanisms Linking Obesity and Diabetes? Implications for Cardiovascular Risk

Cited by 17 publications

References 141 publications

miR‐4431 targets TRIP10/PRKD1 and impairs glucose metabolism

miR‐4431 targets TRIP10/PRKD1 and impairs glucose metabolism

High plasma renin activity associates with obesity-related diabetes and arterial hypertension, and predicts persistent hypertension after bariatric surgery

Recent progress in epigenetics of obesity

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