Expression profiling and analysis of some miRNAs in subcutaneous white adipose tissue during development of obesity

Abstract

Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management Method A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at intervals 2 weeks, serum lipid, hormone levels, total body fat mass, and inguinal subcutaneous white adipose tissue mass (WAT) measurements were recorded using dual-energy X-ray absorptiometry (DEXA). The expression levels of microRNAs were evaluated using real-time PCR. Results Significant alterations were observed in serum glucose, lipid profile, and adipokine hormones during the early stages of obesity development. Alteration in rno-mir 30a-5p, rno-mir 133a-5p, and rno-mir 107-5p expression levels were observed at more than one time point. While rno-let-7a-5p, rno-mir 193a-5p, and rno-mir125a-5p were downregulated and rno-mir130a-5p was upregulated at all time points within 2 to 4 weeks in response to H.F.D feeding for 10 weeks. The impact of switching to normal diet has a reversed effect on lipid profile, adipokine hormone levels, and some miRNAs. The bioinformatics results have identified a novel and important pathway related to inflammatory signalling. Conclusion Our research demonstrated significant alterations in some adipocyte-expressed miRNAs after a short time of high caloric diet consumption. This provides further evidence of the significant role of nutrition as an epigenetic factor in regulation of lipid and glucose metabolism genes by modulating of related key miRNAs. Therefore, we suggest that miRNAs could be used as biomarkers for adiposity during diet-induced obesity. Perhaps limitation in calories intake is a way to manipulate obesity and associated metabolic disorders. Further studies are needed to fully elucidate the role of microRNAs in the development of obesity

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population

“…In our study, interaction effects on T2DM have been demonstrated between miR-133a-2 rs13040413 or let-7a-1 rs13293512 and dyslipidemia. It has been showed that the expression levels of miR-133a and let-7a were in a dysregulation pattern under high lipid condition ( 35 ). Evidence also showed that miR-133a and let-7a were also related to lipid accumulation ( 36 , 37 ).…”

Regulatory microRNAs in Brown, Brite and White Adipose Tissue

“…Furthermore, the Let-7 family is reported to target high-mobility group AT-hook 2 (HMGA2) and is considered involved in adipogenesis, glucose metabolism, insulin resistance, and inflammation [ 133 , 134 ]. A recent study by Youssef et al showed that Let-7 is an important regulator of adipogenesis in 3T3-L1 cells, with Let-7a-5p being downregulated in HFD-fed rats [ 135 ]. Let-7 is upregulated after induction of adipogenesis by either the standard adipogenic cocktail containing dexamethasone, isobutylmethylxanthine, and insulin or the combination of rosiglitazone and insulin [ 133 ].…”

“…Increasing data show that this differentiation of pre-adipocytes is further characterized by changes in the miRNA expression profile of WAT, including both upregulated miRNAs (e.g., MiR-103, MiR-107, MiR-143, MiR-26b, MiR-375, MiR-21, MiR-148a, and MiR-30) [ 94 , 142 , 143 , 144 , 145 , 146 , 147 ] and downregulated miRNAs (e.g., MiR-221, MiR-155, MiR-424, MiR-210, and MiR-125b) [ 143 , 148 , 149 ]. As WAT and BAT adipogenesis share common pathways, there is an overlap in the miRNAs identified in both WAT and BAT, which mediate various effects [ 51 , 135 ].…”

“…Thus, this DNA methylation may attenuate MiR-30 expression, suggesting important roles for miRNAs and DNA methylation in the regulation of adipose tissue macrophage polarization and obesity-induced insulin resistance [ 153 ]. Finally, Youssef et al have shown that MiR-30a-5p targets genes implicated in AMPK signaling, with a HFD resulting in downregulation of this miRNA [ 135 ].…”

Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

“…As a primary regulator of lipid and glucose metabolism (Youssef et al. 2020 ), miR-107-5b is also involved in the formation of cholesterol. Studies have found that miR-107-5b can affect the pathogenesis of cholesterol gallstones (Qian et al.…”