好色先生

I魏B kinase 尾 (IKK尾), a central coordinator of inflammation through activation of nuclear factor-魏B, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKK尾 and found that IKK尾 ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKK尾 ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKK尾 signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKK尾 in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of adipose progenitor IKK尾 signaling in diet-induced obesity, we generated mice that selectively lack IKK尾 in the white adipose lineage and confirmed the essential role of IKK尾 in mediating adipocyte differentiation in vivo. Deficiency of IKK尾 decreased HF-elicited adipogenesis in addition to reducing inflammation and protected mice from diet-induced obesity and insulin resistance. Further, pharmacological inhibition of IKK尾 also blocked human adipose stem cell differentiation. Our findings establish IKK尾 as a pivotal regulator of adipogenesis and suggest that overnutrition-mediated IKK尾 activation serves as an initial signal that triggers adipose progenitor cell differentiation in response to HF feeding. Inhibition of IKK尾 with antisense therapy may represent as a novel therapeutic approach to combat obesity and metabolic dysfunctions. Stem Cells 2016