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Recently, the trend of obesity is becoming increasingly prevalent, and the underlying pathogenesis of obesity is complex and needs to be researched further. In this study, we report a decreased expression of let-7a-5p in the white adipose tissue (WAT) of animals with obesity. Using the RNA oligo, let-7a-5p over-expression or suppression-expression is achieved, impacting the proliferation and differentiation of preadipocytes in vitro. Srebf2 mechanistically interacts with the metabolic effect of let-7a-5p and participates in lipid accumulation by regulating Srebf2 downstream signaling. Moreover, let-7a-5p binds to Thbs1 to interact with the PI3K-AKT-mTOR pathway, down-regulating the phosphorylation levels of AKT, mTOR, and S6K1 to decrease lipid accumulation. In conclusion, our study highlights the physiological significance of let-7a-5p in lipid accumulation and suggests that the let-7a-5p/Srebf2 and let-7a-5p/Thbs1/PI3K-AKT-mTOR axes may represent potential mechanisms for controlling lipid accumulation in obesity.

White adipose tissue (WAT) is important for regulating the whole systemic energy homeostasis. Excessive WAT accumulation further contributes to the development of obesity and obesity-related illnesses. More detailed mechanisms for WAT lipid metabolism reprogramming, however, are still elusive. Here, we report the abnormally high expression of a circular RNA (circRNA) mmu_circ_0001874 in the WAT and liver of mice with obesity. mmu_circ_0001874 interference achieved using a specific adeno-associated virus infects target tissues, down-regulating lipid accumulation in the obesity mice WAT, and liver tissues. Mechanistically, miR-24-3p directly interacts with the lipid metabolism effect of mmu_circ_0001874 and participates in adipogenesis and lipid accumulation by targeting Igf2/PI3K-AKT-mTOR axis. Moreover, mmu_circ_0001874 binds to Igf2bp2 to interact with Ucp1, up-regulating Ucp1 translation and increasing thermogenesis to decrease lipid accumulation. In conclusion, our data highlight a physiological role for circRNA in lipid metabolism reprogramming and suggest mmu_circ_0001874/miR-24-3p/Igf2/PI3K-AKT-mTOR and mmu_circ_0001874/Igf2bp2/Ucp1 axis may represent a potential mechanism for controlling lipid accumulation in obesity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Obesity, a major global health issue, is increasingly associated with the integral role of long non-coding RNA (lncRNA) in adipogenesis. Recently, we found that lncRNA-MSTRG4710 was highly expressed in the liver of rabbits fed a high-fat diet, but whether it is involved in lipid metabolism remains unclear. A series of experiments involving CCK-8, EDU, qPCR, and Oil Red O staining demonstrated that the overexpression of MSTRG4710 stimulated the proliferation and differentiation of preadipocytes while its knockdown inhibited these processes. Bioinformatics analysis showed that miR-29b-3p was a potential target gene of MSTRG4710, and IGF1 was a downstream target gene of miR-29b-3p. Luciferase reporter gene analysis and qPCR analysis confirmed that miR-29b-3p was a potential target gene of MSTRG4710, and miR-29b-3p directly targeted the 3′UTR of IGF1. The overexpression of miR-29b-3p was observed to regulate IGF1 protein and mRNA levels negatively. Additionally, a total of 414 known differentially expressed genes between the miR-29b-3p mimic, miR-29b-3p negative control (NC), siMSTRG4710, and siMSTRG4710-NC group were screened via transcriptome sequencing technology. The GO- and KEGG-enriched pathways were found to be related to lipid metabolism. The study also established that miR-29b-3p targets IGF1 to inhibit preadipocyte proliferation and differentiation. Notably, IGF1 knockdown significantly reduced preadipocyte proliferation and differentiation. Furthermore, co-transfection of pcDNA3.1(+)-MSTRG4710 and mimics into rabbit preadipocytes revealed that the mimics reversed the promotional effect of pcDNA3.1(+)-MSTRG4710. In conclusion, these results uncover that MSTRG4710 positively regulated cell proliferation and adipogenesis by the miR-29b-3p/IGF1 axis. Our findings might provide a new target for studying adipogenesis in rabbit preadipocytes and obesity. [ABSTRACT FROM AUTHOR]

Obesity has become a major health problem worldwide, and increasing evidence supports the importance of microRNAs (miRNAs) in its pathogenesis. Recently, we found that miR-383-5p_1 is highly expressed in the perirenal fat of high-fat-fed rabbits, but it is not yet known whether miR-383-5p is involved in lipid metabolism. Here, we used transcriptome sequencing technology to screen 1642 known differentially expressed genes between miR-383-5p mimic groups and miR-383-5p negative control groups. Gene Ontology Resource (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched in the pathway related to lipid metabolism, and glycine biosynthesis, the NOD receptor signal pathway and nonalcoholic fatty liver were significantly enriched. Afterwards, our research results indicated that miR-383-5p can promote the proliferation and differentiation of rabbit preadipocytes, and there is a direct targeting relationship with RAD51AP1. Mechanistically, miR-383-5p directly interacts with the lipid metabolism and participates in adipogenesis and lipid accumulation by targeting RAD51AP1. In conclusion, our data highlight a physiological role for miRNA in lipid metabolism and suggest the miR-383-5p/RAD51AP1 axis may represent a potential mechanism for controlling lipid accumulation in obesity. [ABSTRACT FROM AUTHOR]