Inhibition of SREBP Transcriptional Activity by a Boron-Containing Compound Improves Lipid Homeostasis in Diet-Induced Obesity

Zhao, Xiaoping; Xiaoli,; Zong, Haihong; Abdulla, Arian; Yang, Eun Kyung; Wang, Qun; Ji, Jun-Yuan; Pessin, Jeffrey E.; Das, Bhaskar; Yang, Fajun

doi:10.2337/db13-0835

Cited by 51 publications

(33 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The three SREBP isoforms, SREBP-1a, SREBP-1c and SREBP-2, play different roles in lipid synthesis. Studies using transgenic and knockout mice suggest that SREBP-1c plays an essential role in the regulation of most lipogenic genes involved in fatty acid and TAG synthesis (Zhao et al, 2014). The present study showed significant increase in SREBP-1c mRNA level as well as FAS activity in the liver tissues of HFD fed rats when compared to treated groups, however dandelion and or milk thistle supplementations attenuated this increase in treated groups.…”

Section: Discussioncontrasting

confidence: 50%

See 1 more Smart Citation

Taraxacum officinale and Silybum marianum alone or combined orchestrate experimentally induced hepatic steatosis through lipogenecity, glucose tolerance and oxidant/antioxidant status

Soliman¹,

El-Dardiry²

2015

Int. J. Bio. Chem. Sci

View full text Add to dashboard Cite

Natural products with a long history of safety can modulate obesity. Taraxacum officinale, known as (dandelion) and Silybum marianum known as (milk thistle) have garnered attention for their antioxidant and antiobesity activities. The present study was conducted to evaluate the potential role of dandelion and milk thistle alone or combined against high fat diet (HFD) induced steatohepatitis. 60 male albino rats which were equally subdivided into four groups: group I was received only HFD, other groups (II, III, IV) were received dandelion, milk thistle or dandelion/milk thistle combination respectively for 8 weeks alongside HFD. Insulin resistance, glucose tolerance, lipogenesis and antioxidant capacity were evaluated in the liver tissue. HFD fed rats exhibited increased insulin resistance-related biomarkers, H 2 O 2 level, mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) as well as fatty acid synthase (FAS) activity with decreased reduced glutathione (GSH) level. Herbal supplementation improved those results with best results were for dandelion/milk thistle combination group. Results were confirmed with histopathological examination. Both dandelion and milk thistle alone or combined improved glucose tolerance and insulin sensitivity, decreased lipogenesis and increased antioxidant capacity with best results obtained in dandelion/milk thistle combination group, implying a potential application in the treatment of hepatic steatosis associated obesity.

show abstract

Section: Discussioncontrasting

confidence: 50%

“…Sterol regulatory element binding proteins (SREBPs) are master transcription factors for de novo lipogenesis (Zhao et al, 2014). The three SREBP isoforms, SREBP-1a, SREBP-1c and SREBP-2, play different roles in lipid synthesis.…”

Section: Discussionmentioning

confidence: 99%

Taraxacum officinale and Silybum marianum alone or combined orchestrate experimentally induced hepatic steatosis through lipogenecity, glucose tolerance and oxidant/antioxidant status

Soliman¹,

El-Dardiry²

2015

Int. J. Bio. Chem. Sci

View full text Add to dashboard Cite

show abstract

“…Such a concept is supported by the results of recent studies on SREBP inhibitors in animal models [43][44][45][46]. Here, we briefly describe the SREBP maturation pathway, elaborate key molecular mechanisms involved in the classical triad of hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, and discuss beneficial effects of four SREBP inhibitors as well as potential caveats associated with their use.…”

mentioning

confidence: 86%

“…The fourth study used a compound that targeted the transcriptional activity of SREBPs [46]. Previous studies have shown that recruitment of the Mediator of RNA polymerase II transcription subunit 15 (MED15)-Kinase-inducible domain interacting (KIX) domain of the mediator complex to the SREBP transactivation domain is necessary for transcriptional activities of SREBPs [76].…”

Section: Bf175mentioning

confidence: 98%

Targeting SREBPs for treatment of the metabolic syndrome

Soyal

Nofziger

Dossena

et al. 2015

Trends in Pharmacological Sciences

View full text Add to dashboard Cite

“…15,16 Sterol regulatory elements (SRE) are cis-regulatory elements present in the promoters of genes that represent the key steps of lipid biosynthesis pathways. The defined SREBP-target genes can be functionally categorized into two groups.…”

Section: Introductionmentioning

confidence: 99%

p54nrb/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A

Zhu

Zhao

et al. 2015

Oncogene

View full text Add to dashboard Cite

Dysregulation of lipid metabolism is common in breast cancer. However, the underlying mechanisms remain elusive and the contribution of aberrant lipid metabolism to the malignant phenotypes of breast cancer is poorly understood. Here, we show that the nuclear protein p54(nrb)/Nono is highly expressed in breast cancer tissues as compared with the adjacent normal tissues in human patients. To determine the functions of p54(nrb) in breast cancer, we performed a biochemical screen and identified SREBP-1a, a master activator for genes involved in lipid biosynthesis, as a novel interacting protein of p54(nrb). In human breast cancer tissues, the levels of p54(nrb) and SREBP-1a proteins were positively correlated with each other. Our biochemical analyses showed that the conserved Y267 residue of p54(nrb) was required for its binding to the nuclear form of SREBP-1a. Interestingly, p54(nrb) binding to nuclear SREBP-1a caused an increase of nuclear SREBP-1a protein stability. As a result, p54(nrb) stimulates SREBP-1-meidated transcription of lipogenic genes and lipid production in breast cancer cells. Moreover, both p54(nrb) and SREBP-1a were required for breast cancer cell growth in vitro, and p54(nrb) binding to nuclear SREBP-1a was also critical for breast tumor development in vivo. Together, we conclude that p54(nrb) is a novel regulator of SREBP-1a in the nucleus, and our data suggest that p54(nrb) regulation of SREBP-1a supports the increased cellular demand of lipids for breast cancer growth. Thus, the SREBP pathway may represent a novel target for treating breast cancer.

show abstract

Inhibition of SREBP Transcriptional Activity by a Boron-Containing Compound Improves Lipid Homeostasis in Diet-Induced Obesity

Cited by 51 publications

References 48 publications

<i>Taraxacum officinale</i> and <i>Silybum marianum</i> alone or combined orchestrate experimentally induced hepatic steatosis through lipogenecity, glucose tolerance and oxidant/antioxidant status

<i>Taraxacum officinale</i> and <i>Silybum marianum</i> alone or combined orchestrate experimentally induced hepatic steatosis through lipogenecity, glucose tolerance and oxidant/antioxidant status

Targeting SREBPs for treatment of the metabolic syndrome

p54nrb/NONO regulates lipid metabolism and breast cancer growth through SREBP-1A

Contact Info

Product

Resources

About