SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling

Wang, Hongrui; Yu, Liang; Wang, Jin’e; Zhang, Yaqing; Xu, Mengchen; Lv, Cheng; Cui, Bing; Yuan, Mengmeng; Zhang, Yu; Yan, Yupeng; Hui, Rutai; Wang, Yibo

doi:10.1038/s41467-023-43418-5

Cited by 3 publications

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that the activation of Notch1 signaling promotes adipocyte proliferation [ 19 ], while the modulation of the Notch1 signal in adipose tissue macrophages is crucial for regulating inflammation and metabolism [ 20 ]. Moreover, inhibiting Notch1 expression has been shown to significantly enhance brown fat thermogenesis, promote white fat browning, and ameliorate obesity [ 21 , 22 , 23 ]. Although EGCG can improve inflammation by inhibiting Notch1 and has significant effects on obesity [ 11 , 24 ], it is still uncertain whether EGCG in adipose tissue can have the same metabolic-promoting and obesity-improving effects by targeting Notch1.…”

Section: Introductionmentioning

confidence: 99%

EGCG Suppresses Adipogenesis and Promotes Browning of 3T3-L1 Cells by Inhibiting Notch1 Expression

Wang,

Li,

Peng

et al. 2024

Molecules

View full text Add to dashboard Cite

Background: With the changes in lifestyle and diet structure, the incidence of obesity has increased year by year, and obesity is one of the inducements of many chronic metabolic diseases. Epigallocatechin gallate (EGCG), which is the most abundant component of tea polyphenols, has been used for many years to improve obesity and its complications. Though it has been reported that EGCG can improve obesity through many molecular mechanisms, EGCG may have many mechanisms yet to be explored. In this study, we explored other possible mechanisms through molecular docking and in vitro experiments. Methods: AutoDock Vina was selected for conducting the molecular docking analysis to elucidate the interaction between EGCG and Notch1, while molecular dynamics simulations were employed to validate this interaction. Then, the new regulation mechanism of EGCG on obesity was verified with in vitro experiments, including a Western blot experiment, immunofluorescence experiment, oil red O staining, and other experiments in 3T3-L1 adipocytes. Results: The molecular docking results showed that EGCG could bind to Notch1 protein through hydrogen bonding. In vitro cell experiments demonstrated that EGCG can significantly reduce the sizes of lipid droplets of 3T3-L1 adipocytes and promote UCP-1 expression by inhibiting the expression of Notch1 in 3T3-L1 adipocytes, thus promoting mitochondrial biogenesis. Conclusions: In this study, molecular docking and in vitro cell experiments were used to explore the possible mechanism of EGCG to improve obesity by inhibiting Notch1.

show abstract

Section: Introductionmentioning

confidence: 99%

EGCG Suppresses Adipogenesis and Promotes Browning of 3T3-L1 Cells by Inhibiting Notch1 Expression

Wang,

Li,

Peng

et al. 2024

Molecules

View full text Add to dashboard Cite

show abstract

Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice

Li,

Ye,

Zhao

et al. 2024

Front. Physiol.

View full text Add to dashboard Cite

BackgroundLing-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity.MethodsMale C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting.ResultsThe results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues.ConclusionOur findings position LGZG as a novel strategy for preventing obesity and improving metabolic health.

show abstract

Solute Carrier Family 35 (SLC35)—An Overview and Recent Progress

Kamiyama,

Sone

2024

Biologics

View full text Add to dashboard Cite

The solute carrier family 35 (SLC35) comprises multiple members of transporters, including a group of proteins known as nucleotide sugar transporters (NSTs), an adenosine triphosphate (ATP) transporter, 3′-phosphoadenosine 5′-phosphosulfate (PAPS) transporters, and transporters of unknown function. To date, seven subfamilies (A to G) and 32 members have been classified into this large SLC35 family. Since the majority of glycosylation reactions occur within the lumen of the endoplasmic reticulum (ER) and Golgi apparatus, the functions of NSTs are indispensable for the delivery of substrates for glycosylation. Recent studies have revealed the diverse functions of this family of proteins in the regulation of numerous biological processes, including development, differentiation, proliferation, and disease progression. Furthermore, several congenital disorders of glycosylation (CDGs) resulting from variations in the SLC35 family member genes have been identified. To elucidate the pathology of these diseases, a variety of knockout mice harboring mutations in the family member genes have been generated and employed as animal models for CDGs. This review presents a historical overview of the SLC35 family, with a particular focus on recent advances in research on the functions of this family and their relationship to human diseases.

show abstract

SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling

Cited by 3 publications

References 53 publications

EGCG Suppresses Adipogenesis and Promotes Browning of 3T3-L1 Cells by Inhibiting Notch1 Expression

EGCG Suppresses Adipogenesis and Promotes Browning of 3T3-L1 Cells by Inhibiting Notch1 Expression

Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice

Solute Carrier Family 35 (SLC35)—An Overview and Recent Progress

Contact Info

Product

Resources

About