Abstract
BackgroundWe have shown previously that microvesicle (MV)-delivered miR-130b (miR-130b-MV) is able to target PPAR-γ and subsequently reduce the lipid accumulation in vitro. However, the in vivo effect of miR-130b on fat deposition and glucose homeostasis remains unknown.ResultsThree-week-old C57BL/6 mice were fed a high-fat diet for 8 weeks and then intravenously injected with MV-packaged scrambled control microRNA (miRNA) or miR-130b every other day for 10 days. Glucose tolerance test was performed and body weight, epididymal fat weight, as well as the expression of lipid metabolic genes were determined. We showed that mice fed on high-fat diet for 8 weeks demonstrated significantly higher body weight, elevated blood glucose and impaired glucose tolerance. miR-130b-MV injection significantly reduced body weight and epididymal fat weight and partly restored glucose tolerance. miR-130b expression was significantly increased in the epididymal fat after miR-130b-MV injection while the protein content of its target gene PPAR-γ was significantly suppressed, together with a significant up-regulation of the lipolysis genes, hormone sensitive lipase, monoglyceride lipase and leptin. Moreover, miR-130b-MV injection increased the expression of miR-378a and miR-378-3p that are reported to participate in the regulation of fat deposition.ConclusionOur results indicate that miR-130b-MV is able to reduce the epididymal fat deposition and partly restore glucose tolerance, through translational repression of PPAR-γ in a high-fat diet-induced obese mouse model.
Highlights
We have shown previously that microvesicle (MV)-delivered miR-130b is able to target Peroxisome proliferators-activated receptor-γ (PPAR-γ) and subsequently reduce the lipid accumulation in vitro
We show that miR-130b was delivered to the epididymal fat tissue and significantly decreased the fat deposition, which was associated with a significant down-regulation of PPAR-γ protein content and an activation of lipolytic genes
Establishment of high-fat diet-induced obese mouse model C57BL/6 obese mouse model was successfully established after feeding high-fat diet ad libitum for 8 weeks (Fig. 1)
Summary
We have shown previously that microvesicle (MV)-delivered miR-130b (miR-130b-MV) is able to target PPAR-γ and subsequently reduce the lipid accumulation in vitro. Peroxisome proliferator activated receptor gamma (PPAR-γ) is a ligand activated transcription factor which is regarded as a master regulator of fat deposition [6,7,8]. Previous studies have shown that activation or over-expression of PPAR-γ can stimulate lipogenesis and adipogenesis [1], while down-. Numerous studies have demonstrated that some miRNAs can inhibit PPARγ expression and suppress adipogenesis and lipogenesis. Both miR-302a and miR-27a are reported to inhibit adipogenic differentiation and lipid accumulation in 3T3-L1 mouse adipocytes [15] and human multipotent adiposederived stem cells [16] by down-regulating PPAR-γ expression. MiR-130 has been shown to strongly reduce adipogenesis by repressing PPAR-γ biosynthesis in human primary preadipocytes and 3T3-L1 mouse adipocytes Both miR-302a and miR-27a are reported to inhibit adipogenic differentiation and lipid accumulation in 3T3-L1 mouse adipocytes [15] and human multipotent adiposederived stem cells [16] by down-regulating PPAR-γ expression. miR-130 has been shown to strongly reduce adipogenesis by repressing PPAR-γ biosynthesis in human primary preadipocytes and 3T3-L1 mouse adipocytes
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