miR-129-5p Inhibits Adipogenesis through Autophagy and May Be a Potential Biomarker for Obesity

Abstract

Introduction Obesity has an unclear pathogenesis. MicroRNAs (miRNAs) may function as biologically active molecules for obesity through regulating adipocyte differentiation. This study aimed to identify how miR-129-5p (a specific miRNA) regulates adipogenesis in vitro and explore its possible role in the pathogenesis of obesity in humans. Materials and Methods The miR-129-5p expression was detected in obese mouse models. The effect of miR-129-5p on adipocyte differentiation was observed, and the adipose markers were analyzed. Bioinformatics and dual-luciferase reporter assay were applied to predict and confirm the target genes of miR-129-5p. The human serum samples were detected and analyzed. Results miR-129-5p is highly expressed in adipose tissues of db/db mice. Gain- and loss-of-function studies show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets ATG7 which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay. Serum miR-129-5p level was evidently elevated in patients with simple obesity (p < 0.01) and correlates with obesity indices, including BMI (r = 0.407, p < 0.029) and fat percentage (r = 0.394, p < 0.038). Conclusion miR-129-5p might target on the ATG7-related autophagy signaling network that regulates white and brown adipogenesis. Importantly, the aforementioned results suggest serum miR-129-5p might be a potential biomarker and therapeutic target for obesity.

WITHDRAWN: Dysregulation of miR-129-5p in Patients with Non-Alcoholic Fatty Liver Disease and Its Regulatory Effect on Insulin Resistance

“…As expected, downregulation of miR-129-5p reversed the in uence of NAFLD on lipid metabolism and insulin sensitivity in NAFLD mice model. Supportably, in obese mouse models, miR-129-5p is suggested to be highly expressed in the white adipose tissue of model mouse and inhibits the differentiation of brown fat adipogenesis, which contributes to obesity and development of IR [15]. Combining the presents results and previous evidence, we concluded that the regulatory effect of miR-129-5p on NAFLD may function by regulating lipid accumulation and insulin sensitivity.…”

“…Consistently, elevated expression of miR-129-5p has been reported in subjects with obesity and serves as a promising biomarker for the occurrence of obesity, which contributes to the development of NAFLD [15]. In addition, miR-129-5p has also been demonstrated to be involved in the process of metabolic diseases, such as diabetes mellitus, islets damage [23,24].…”

“…Moreover, the high stability of miRNAs in blood and tissues has been con rmed, and many circulating miRNAs have been used for non-invasive detection and treatment of many diseases [13,14]. Fu X et al have studied the role of miR-129-5p in obese individuals, and found that miR-129-5p is highly expressed in both obese individuals and animal models, and obesity is known to be the risk factor for the occurrence of NAFLD [15]. However, the role and regulatory mechanisms of miR-129-5p in NAFLD remain largely unknown.…”

Regulatory microRNAs in Brown, Brite and White Adipose Tissue

“…This miRNA targets both Igf2 (insulin like growth factor 2) and Egr1 (Early growth factor response 1), with both these factors being UCP1 inhibitors [ 92 , 112 ]. A recent study by Fu et al showed that MiR-129 also directly targets ATG7 (Autophagy-related gene 7), which is an essential autophagy gene [ 89 ]. Indeed, this study showed that MiR-129-5p inhibits adipogenesis by autophagy, demonstrating increased expression of MiR-129-5p in the AT of db / db mice.…”

Eugenol Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Autophagy via AMPK-mTOR-P70S6K Pathway

“…Autophagy, as a basic biological process that degrades and recycles damaged organelles and intracellular macromolecules, participates in multiple pathological and physiological processes. It has been documented that autophagy takes part in the progression of various diseases, such as neurodegenerative disorders (Kumar et al, 2018), diabetes (Barlow and Thomas, 2015), obesity (Fu et al, 2019), and so on. Notably, growing evidence has indicated that autophagy is also involved in many ischemic diseases, including myocardial infarction (Aisa et al, 2017), renal ischemia reperfusion injury (Hou et al, 2019), and cerebral ischemia reperfusion injury (Zhang et al, 2013), etc.…”