scholarly journals Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression

Theranostics ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 3501-3514 ◽  
Author(s):  
Zhuanghui Feng ◽  
Yuda Wei ◽  
Yongxian Zhang ◽  
Yan Qiu ◽  
Xiaojian Liu ◽  
...  

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.



Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1703-P
Author(s):  
SVETLANA MICHURINA ◽  
IURII STAFEEV ◽  
IGOR SKLYANIK ◽  
EKATERINA SHESTAKOVA ◽  
ANATOLIY YURASOV ◽  
...  


Phenomics ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 15-21
Author(s):  
Yan Qiu ◽  
Xiaojian Liu ◽  
Yingmin Sun ◽  
Shuang Li ◽  
Yuda Wei ◽  
...  


RSC Advances ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 160-163
Author(s):  
Zijing Li ◽  
Bin Huang ◽  
Yuan Wang ◽  
Wenbo Yuan ◽  
Yijing Wu ◽  
...  

2RDNTPA can be applied in fluorescence imaging of living cancer cells (HepG2) with red emission of 620 nm and negligible cytotoxicity with a half maximal inhibitory concentration much more than 100 μM.



Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 111
Author(s):  
Eunhee Cho ◽  
Da Yeon Jeong ◽  
Jae Geun Kim ◽  
Sewon Lee

Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise-induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin-UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n = 10) and swimming exercise groups (SEG, n = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min. The mRNA and protein expression of PGC-1α, FNDC5 and browning markers including UCP1 were evaluated by quantitative real-time PCR and western blotting. Serum irisin concentration was measured by enzyme-linked immunosorbent assay. An acute swimming exercise did not lead to alterations in the mRNA and protein expression of PGC-1α in both soleus and gastrocnemius muscles, the mRNA and protein expression of UCP1 in brown adipose tissue, mRNA browning markers in visceral adipose tissue and circulating irisin when compared with the control group. On the other hand, an acute swimming exercise led to increases in the mRNA and protein expressions of FNDC5 in the soleus muscle, the protein expression of FNDC5 in the gastrocnemius muscles and the protein expression of UCP1 in subcutaneous adipose tissue.



2016 ◽  
Vol 311 (2) ◽  
pp. E530-E541 ◽  
Author(s):  
Yuan Zhang ◽  
Chao Xie ◽  
Hai Wang ◽  
Robin M. Foss ◽  
Morgan Clare ◽  
...  

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes “browning” of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.



1984 ◽  
Vol 18 ◽  
pp. 368A-368A
Author(s):  
Jean E Robillard ◽  
Kenneth T Nakamura ◽  
Oliva McWeeny ◽  
Sindy Wear ◽  
William Lawton




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