iTRAQ-Based Quantitative Proteomics Analysis of the Protective Effect of Yinchenwuling Powder on Hyperlipidemic Rats
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
Authors: Zhang, Zheyu; Wang, Wenbo; Jin, Ling; Cao, Xin; Jian, Gonghui; Wu, Ning; Xu, Xia; Yao, Ye; Wang, Dongsheng
Abstract
Yinchenwuling powder (YCL) is an effective traditional Chinese medicine formula to modulate lipid levels. In this study, we established hyperlipidemic rat models and treated them with YCL. The serum concentrations of lipid, malondialdehyde (MDA), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) were measured. Adventitia-free vascular proteins between hyperlipidemic rats and YCL-treated rats were identified using iTRAQ-based quantitative proteomics research approach. Proteins with 1.3-fold difference were analyzed through bioinformatics, and proteomic results were verified by Western blot. The results showed that the serum levels of TC, TG, LDL-C, ET-1, and MDA were significantly decreased, whereas the HDL-C and CGRP levels were significantly increased in the YCL-treated group. Proteomics technology identified 4,382 proteins, and 15 proteins were selected on the basis of their expression levels and bioinformatics. Of these proteins, 2 (Adipoq and Gsta1) were upregulated and 13 (C3, C4, C6, Cfh, Cfp, C8g, C8b, Lgals1, Fndc1, Fgb, Fgg, Kng1, and ApoH) were downregulated in the YCL-treated rats. Their functions were related to immunity, inflammation, coagulation and hemostasis, oxidation and antioxidation, and lipidmetabolism and transport. The validated results of ApoH were consistent with the proteomics results. This study enhanced our understanding on the therapeutic effects and mechanism of YCL on hyperlipidemia.
Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds
SCIENTIFIC REPORTS
Authors: Takeda, Yukimasa; Harada, Yoshinori; Yoshikawa, Toshikazu; Dai, Ping
Abstract
Brown adipocytes play an important role in human energy metabolism and prevention of obesity and diabetes. Induced pluripotent stem cells (iPSCs) represent a promising source for brown adipocytes; however, exogenous gene induction is generally required for iPSCs generation, which might cause undesired effects particularly in long-term treatment after transplantation. We have previously reported a cocktail of six small chemical compounds that enables a conversion of human fibroblasts into chemical compound-induced neuronal cells (CiNCs). Here, we report that modified combinations of the chemical compounds and rosiglitazone, a PPAR gamma agonist, afforded direct conversion of human fibroblasts into brown adipocytes. The chemical compound-induced brown adipocytes (ciBAs) exhibit induction of human brown adipocyte-specific genes such as Ucp1, Ckmt1, Cited1 and other adipocytespecific genes such as Fabp4, AdipoQ, and Ppar gamma. Treatment with either isoproterenol or Forskolin further induced the expression of Ucp1, suggesting that beta adrenergic receptor signalling in ciBAs could be functional for induction of thermogenic genes. Moreover, oxygen consumption rates were elevated in ciBAs along with increase of cellular mitochondria. Our findings might provide an easily accessible approach for generating human brown adipocytes from fibroblasts and offer therapeutic potential for the management of obesity, diabetes, and related metabolic disorders.