Adipocyte-based high throughput screening for anti-obesity drug discovery: Current status and future perspectives

Tsui, Leo

doi:10.1016/j.slasd.2022.08.001

Cited by 6 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past several hundred years, bioactive compounds from medicinal plants have emerged as alternatives to conventional obesity treatments. As a potential candidate for the development of anti-obesity drugs, research on the molecular mechanisms of action of compounds derived from medicinal plants is being intensively conducted [ 4 , 6 ]. Recently, natural compounds for the browning of white adipocytes have been intensively investigated [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, various methods such as diet therapy, exercise therapy, lifestyle modification, drug therapy, and surgical treatment have been implemented to treat obesity. Many anti-obesity drugs are being developed every year for the treatment of obesity; however, due to various side effects, currently available anti-obesity drugs are limited [ 4 , 5 ]. In addition, most anti-obesity drugs are limited to appetite suppressants, classified as psychotropic drugs and digestive suppressants, with side effects such as diarrhea and constipation.…”

Section: Introductionmentioning

confidence: 99%

“…Adipocytes, which play an important role in energy homeostasis, are closely related to metabolic diseases such as obesity and diabetes [ 4 ]. In the study of obesity control mechanisms, strategies for the potential treatment of obesity and related diseases in the browning of white adipose tissue have been selected in recent years.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Park

Kang

et al. 2022

IJMS

View full text Add to dashboard Cite

The mechanism of white adipose tissue browning is not well understood; however, naturally occurring compounds are known to play a positive role. The effects of cucurbitacins B, E, and I on the browning of mature white adipocytes were investigated. First, the cell viability exhibited by cucurbitacins B, E, and I in pre- and mature adipocytes was verified. Cucurbitacins B, E, and I had no effect on cell viability in pre- and mature adipocytes at concentrations up to 300 nM. To investigate the characteristics of representative beige adipocytes, the formation and morphology of cucurbitacin B, E, and I lipid droplets were verified. The total lipid droplet surface area, maximum Feret diameter, and total Nile red staining intensity of cucurbitacin B-, E-, and I-treated adipocytes were lower than those of mature white adipocytes. Furthermore, treatment of white mature adipocytes with cucurbitacin B, E, and I led to the formation of several small lipid droplets that are readily available for energy expenditure. We evaluated the effect of cucurbitacins B, E, and I on the expression of representative browning markers UCP1, PGC1a, and PRDM16, which participate in the browning of white adipose tissue. Cucurbitacins B, E, and I increased the mRNA and protein expression levels of UCP1, PGC1a, and PRDM16 in a concentration-dependent manner. To promote energy consumption by beige adipocytes, active mitochondrial biogenesis is essential. Next, we investigated the effects of cucurbitacin B, E, and I on mitochondrial biogenesis in mature adipocytes. Mitochondrial mass increased when mature adipocytes were treated with cucurbitacin B, E, and I. The degree of cucurbitacin B-, E- and I-induced transformation of white adipocytes into beige adipocytes was in the order of Cu E > Cu B > Cu I. To verify the effect of phospholipase D2 on the browning of white adipocytes, CAY10594—a PLD2 pharmacological inhibitor, and a knockdown system were used. PLD2 inhibition and knockdown improved the expression levels of UCP1, PGC1a, and PRDM16. In addition, PLD2 inhibition and knockdown in mature white adipocytes promoted mitochondrial biosynthesis. The effect of PLD2 inhibition and knockdown on promoting browning of white adipocytes significantly increased when Cu B, Cu E, and Cu I were co-treated. These data indicate that mature white adipocytes’ beige properties were induced by cucurbitacins B, E, and I. These effects became more potent by the inhibition of PLD2. These findings provide a model for determining anti-obesity agents that induce browning and increase energy expenditure in mature white adipocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Park

Kang

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Previous adipocyte‐based screening systems have been influenced by morphological changes and lipid droplets in adipocytes. They did not accurately reflect the differentiation of beige adipocytes [17]. To overcome these obstacles, we exposed the adipocytes to the compounds before and after adipogenic induction and performed three consecutive screenings to identify hit candidates.…”

Section: Introductionmentioning

confidence: 99%

A newly identified compound activating UCP1 inhibits obesity and its related metabolic disorders

Onodera,

Hasegawa,

Yokota

et al. 2023

Obesity

View full text Add to dashboard Cite

ObjectivePromoting thermogenesis in adipose tissue has been a promising strategy against obesity and related metabolic complications. We aimed to identify compounds that promote thermogenesis in adipocytes and to elucidate their functions and roles in metabolism.MethodsTo identify compounds that directly promote thermogenesis from a structurally diverse set of 4800 compounds, we utilized a cell‐based platform for high‐throughput screening that induces uncoupling protein 1 (Ucp1) expression in adipocytes.ResultsWe identified one candidate compound that activates UCP1. Additional characterization of this compound revealed that it induced cellular thermogenesis in adipocytes with negligible cytotoxicity. In a subsequent diet‐induced obesity model, mice treated with this compound exhibited a slower rate of weight gain, improved insulin sensitivity, and increased energy expenditure. Mechanistic studies have revealed that this compound increases mitochondrial biogenesis by elevating maximal respiration, which is partly mediated by the protein kinase A (PKA)‐p38 mitogen‐activated protein kinase (MAPK) signaling pathway. A further comprehensive genetic analysis of adipocytes treated with these compounds identified two novel UCP1‐dependent thermogenic genes, potassium voltage‐gated channel subfamily C member 2 (Kcnc2) and predicted gene 5627 (Gm5627).ConclusionsThe identified compound can serve as a potential therapeutic drug for the treatment of obesity and its related metabolic disorders. Furthermore, our newly clarified thermogenic genes play an important role in UCP1‐dependent thermogenesis in adipocytes.

show abstract

An in vitro model of adipose tissue-associated macrophages

Bhatia,

Tiwari,

Gupta

et al. 2024

J Biosci

View full text Add to dashboard Cite

Adipocyte-based high throughput screening for anti-obesity drug discovery: Current status and future perspectives

Cited by 6 publications

References 55 publications

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

Cucurbitacin B-, E-, and I-Induced Browning of White Adipocytes Is Promoted by the Inhibition of Phospholipase D2

A newly identified compound activating UCP1 inhibits obesity and its related metabolic disorders

An in vitro model of adipose tissue-associated macrophages

Contact Info

Product

Resources

About