scholarly journals Rheb Inhibits Beiging of White Adipose Tissue via PDE4D5-Dependent Downregulation of the cAMP-PKA Signaling Pathway

Diabetes ◽  
2017 ◽  
Vol 66 (5) ◽  
pp. 1198-1213 ◽  
Author(s):  
Wen Meng ◽  
Xiuci Liang ◽  
Hongzhi Chen ◽  
Hairong Luo ◽  
Juli Bai ◽  
...  
2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Huiying Cong ◽  
Wenxia Zhong ◽  
Yiying Wang ◽  
Shoichiro Ikuyama ◽  
Bin Fan ◽  
...  

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity.


2018 ◽  
Vol 40 (01) ◽  
pp. 57-61 ◽  
Author(s):  
Haitang Wang ◽  
J.- Lee ◽  
Ye Tian

AbstractExercise is recognized as an effective method to prevent obesity and alleviate metabolic diseases. Browning of white adipose has the advantage of decreasing insulin resistance. We aim to identify critical differentially expressed genes (DEGs) in white adipose tissue after exercise. We downloaded the gene dataset GSE68161 of C57BL/6 mice from the Gene Expression Omnibus (GEO) database. Then, we analyzed the effect of exercise on up-regulated and down-regulated DEGs by GEO2R and performed protein-protein interaction network analyses. We then identified hub-genes in white adipose tissue and crosstalk genes of a single pathway by the STRING database and Cytoscape. In this study, 72 DEGs were screened out, and they mainly function in glycerol-3-phosphate dehydrogenase activity and in the primary biological process of fatty acid oxidation regulation. The top 5 hub-genes screened out were SLC27A1, COX7A1, PPARGC1A, FABP3, and UCP1. The 3 crosstalk genes found were SLC27A1, SLC27A2, and PPARA. These 3 genes might function as a bridge of the PPAR signaling pathway, adipocytokine signaling pathway and the insulin resistance pathway. SLC27A1 is critical gene for the interactions of signaling pathways in subcutaneous white adipose tissue. Therefore, further relationships between the browning of white adipose and insulin resistance need to be studied.


2019 ◽  
Vol 38 (11) ◽  
pp. 1303-1312
Author(s):  
Wenting Zhang ◽  
Xiaohui Wu ◽  
Zhou Pei ◽  
Wieland Kiess ◽  
Yan Yang ◽  
...  

2018 ◽  
Vol 51 (6) ◽  
pp. 2900-2915 ◽  
Author(s):  
Chuanhai Zhang ◽  
Jing Jing Wang ◽  
Xiaoyun He ◽  
Chao Wang ◽  
Boyang Zhang ◽  
...  

Background/Aims: Brown and beige adipocytes are widely recognized as potential therapeutic targets to treat obesity and related metabolic disorders, and the recruitment of brown and beige adipocytes is an essential aspect that requires attention. Although many methods of activating brown adipocytes or generating beige adipocytes have been reported, the limited number and sources are the biggest challenges. The number of white adipocytes is much greater than the number of brown adipocytes, both in human adults and fetuses. Unfortunately, human adult white adipose tissue-derived stem cell (aWAsc) has little beige adipogenic potential. However, the characteristics and beige adipogenic potential of human embryo-derived white adipose stem cells (eWAsc) still need to be investigated. Methods: To analyze the characteristics and functionality of eWAsc, we analyzed the markers of adipose precursor cells by flow cytometry. Then, differentiation and browning/beiging were induced, and the identifying markers were analyzed by real-time PCR and immunoblot. In addition, more in-depth exploration was performed using RNA-SEQ on eWAsc and aWAsc. Results: eWAsc was isolated from human embryonic white adipose tissue, and aWAsc was isolated from adult white adipose tissue by collagenase treatment. eWAsc has extreme advantages in adipogenesis capacity and browning/beiging ability in comparison to aWAsc, indicating that eWAsc may possess some special regulatory factors to promote the generation of functional brown/beige adipocytes. Greater exploration was enabled by RNA-SEQ, revealing a large number of differences at the transcriptional levels, including 1263 differentially expressed genes, 657 down- and 605 upregulated, in eWAsc compared to aWAsc. Pathway analysis revealed enrichment in cell cycle, TGF-β signaling pathway, DNA replication, and Hippo signaling pathways. Interestingly, the expression levels of C/EBPα, FGF1 and FST gene, which are related to the maturation of adipocytes, Hippo signaling pathway and TGF-β signaling pathway, were significantly higher in eWAsc than in aWAsc. These may be potential candidates and possible regulatory targets for recruiting beige adipocytes in human adipose tissue. Conclusion: Overall, we have demonstrated the molecular characteristics and excellent beige adipogenic potential of eWAsc, providing a new reference for studying human adipocytes.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1351
Author(s):  
Xujia Zhang ◽  
Siyuan Zhan ◽  
Shizhong Yang ◽  
Tao Zhong ◽  
Jiazhong Guo ◽  
...  

Adipose tissues are mainly divided into brown adipose tissue (BAT) and white adipose tissue (WAT). WAT mainly functions to buffer excess calories, whereas BAT plays a role in the non-shivering thermogenesis to maintain body temperature and energy balance. Moreover, circRNAs play important roles in various biological processes. However, knowledge of the expression profile and function of circRNAs from BAT to WAT remains largely unknown. In this study, a total of 6610 unique circRNAs were identified in the perirenal adipose tissues of 1-day, 30-days, and 1-year goats. Functional annotation revealed that host genes of circRNAs were involved in some BAT-related pathways, such as the thyroid hormone signaling pathway, MAPK signaling pathway, and VEGF signaling pathway. Furthermore, a total of 61 DEcircRNAs were detected across three stages. Additionally, five selected circRNAs were validated by RNase R assay, qPCR, and Sanger sequencing. Finally, the circRNA–miRNA network was constructed between the DEcircRNAs and their miRNA binding sites.


2018 ◽  
Vol 19 (9) ◽  
pp. 2530 ◽  
Author(s):  
Jun Wang ◽  
Lin He ◽  
Bahetiyaer Huwatibieke ◽  
Lingchao Liu ◽  
He Lan ◽  
...  

Adipose tissue is hyper-vascularized. Vessels in adipose tissue not only supply nutrients and oxygen to nourish adipocytes, but also provide cytokines that regulate mass and function of adipose tissue. Understanding the fundamental mechanisms how vessels modulate adipocyte functions would provide new therapeutic options for treatment of metabolic disease and obesity. In recent years, researches about ghrelin are focused on glucose and lipid metabolism, but its effect on vascular function remains uncharacterized. In the present study, ghrelin receptor gene deletion mice (Ghsr−/− mice) were used to study ghrelin-regulated vascular metabolism in white adipose tissue. Ghsr−/− mice demonstrated lower food intake, lower body weight, and resistance to high-fat diet-induced obesity. The number of vessels in white adipose tissue was decreased in Ghsr−/− mice when compared with wild type mice fed with high-fat diet. To further define ghrelin effects in vitro, we used endothelial progenitor cells from wild type and Ghsr−/− mice as well as human umbilical vein endothelial cells in our experiments. We found that ghrelin stimulated endothelial cells angiogenesis and migration through the MEK-ERK signaling pathway. [d-Lys3]-GHRP-6 and PD98059 could reverse the effects of ghrelin on endothelial cells. Our study indicates that ghrelin activates its receptor on endothelial cells to promote angiogenesis and migration via a mechanism involving the extracellular regulated protein kinases (ERK) signaling pathway.


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