Differential Expression of miRNAs by Anti-Obesity Treatment Sulforaphane in Skeletal Muscle of Diet-Induced Obesity in Mice

Abstract

Background: Skeletal muscles comprise 40–60% of the body's total weight and 30% of the metabolic rate at rest. As the primary site for glucose uptake into tissues by insulin induction, it is crucial for metabolic homeostasis in the body. The natural isothiocyanate compound sulforaphane primarily functions as an antioxidant, but numerous studies have revealed that it also has anti-obesity properties. Recent studies have demonstrated that miRNAs are essential in controlling skeletal muscle dysfunction. The objective is to investigate the miRNA expression profile in the skeletal muscles of DIO mice given SFN and to ascertain their function by identifying the metabolic pathways and gene ontologies involved. Methods: Male mice of CD1 strain were randomized at age four weeks and fed a high fat diet to induce diet-induced obesity (DIO) followed by SFN and vehicle treatment for four weeks. Total RNA was extracted from the skeletal muscles of DIO mice, and small RNA sequencing was utilized to identify the microRNA expression profiles. In addition, pathway mapping and gene ontology (GO) tools were used to evaluate the biological processes and signaling pathways affected by the differentially expressed microRNAs. Results: Body weight, food intake, plasma glucose, and leptin levels were all significantly lower in the SFN-treated group compared to the control group. Furthermore, in SFN-treated DIO mice, eight differentially expressed miRNAs were detected, five upregulated (mmu-miR-150-5p, mmu-miR-486a-3p, mmu-miR-126b-5p, mmu-miR-140-3p, mmu-miR-92a-3p) and three of which were downregulated (mmu-miR-101a-3p, mmu-miR-29c-3p, mmu-miR-3074-5p). Furthermore, SFN treatment alters miRNAs that regulate genes involved in insulin signaling, MAPK, and PI3K/Akt signaling pathways, all essential regulators of skeletal muscle metabolism, including insulin resistance and obesity. Conclusion: SFN induced a change in the expression profiles of microRNAs in the skeletal muscle of DIO mice, which regulate gene targets of miRNAs involved in a variety of biological processes that combat obesity. This study was supported by the Qatar National Research Foundation grant (NPRP9-351-3-075) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.