期刊
PHARMACEUTICALS
卷 16, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/ph16010091
关键词
spinophilin; white adipocyte browning; PPAR-gamma; obesity; UCP-1
This study revealed the critical role of SPL in the browning of visceral white adipose tissue (vWAT). SPL knockout (KO) mice exhibited higher expression of classic browning-related genes and mtDNA levels in vWAT compared to wild type (WT) mice. Furthermore, treatment with rosiglitazone induced browning in vWAT of SPL KO mice, resulting in weight loss.
Browning of white adipose tissue (WAT) is suggested as a promising therapeutic approach to induce energy expenditure and counteract obesity and its associated complications. Systemic depletion of spinophilin (SPL) increases metabolism and improves energy balance in mice. In this study, we explored the mechanistic insight of SPL action in WAT browning. Gene expression and mitochondria tracker staining showed that visceral white adipose tissue (vWAT) harvested from SPL KO mice had a higher expression of classic browning-related genes, including uncoupling protein 1 (UCP1), Cell death inducing DFFA like effector A (CIDEA) and PR domain containing 16 (PRDM16), as well as a higher mtDNA level compared to vWAT from wild type (WT) control mice. When adipogenesis was induced in pre-adipocytes harvested from KO and WT mice ex vivo using the PPAR-gamma agonist rosiglitazone (Rosi), SPL KO cells showed increased browning marker gene expression and mitochondria function compared to cells from WT mice. Increased PPAR-gamma protein expression and nucleus retention in vWAT from SPL KO mice after Rosi treatment were also observed. The effect of SPL on vWAT browning was further confirmed in vivo when WT and KO mice were treated with Rosi. As a result, SPL KO mice lost body weight, which was associated with increased expression of browning maker genes in vWAT. In summary, our data demonstrate the critical role of SPL in the regulation of WAT browning.
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