scholarly journals Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

Author(s):  
Won-Il Choi ◽  
Jae-Hyun Yoon ◽  
Seo-Hyun Choi ◽  
Bu-Nam Jeon ◽  
Hail Kim ◽  
...  

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

2020 ◽  
Vol 11 (3) ◽  
pp. 2418-2426 ◽  
Author(s):  
Mailin Gan ◽  
Linyuan Shen ◽  
Shujie Wang ◽  
Zhixian Guo ◽  
Ting Zheng ◽  
...  

Genistein may regulate lipid metabolism in adipose tissue of obese mice by regulating the expression of miR-222 and its target genes, BTG2 and adipor1.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Young-Sil Yoon ◽  
Weiyi Liu ◽  
Sam Van de Velde ◽  
Shigenobu Matsumura ◽  
Ezra Wiater ◽  
...  

AbstractObesity is a major risk factor for the development of type II diabetes. Increases in adipose tissue mass trigger insulin resistance via the release of pro-inflammatory cytokines from adipocytes and macrophages. CREB and the CRTC coactivators have been found to promote insulin resistance in obesity, although the mechanism is unclear. Here we show that high fat diet feeding activates the CREB/CRTC pathway in adipocytes by decreasing the expression of SIK2, a Ser/Thr kinase that phosphorylates and inhibits CRTCs. SIK2 levels are regulated by the adipogenic factor C/EBPα, whose expression is reduced in obesity. Exposure to PPARγ agonist rescues C/EBPα expression and restores SIK2 levels. CRTC2/3 promote insulin resistance via induction of the chemokines CXCL1/2. Knockout of CRTC2/3 in adipocytes reduces CXCL1/2 expression and improves insulin sensitivity. As administration of CXCL1/2 reverses salutary effects of CRTC2/3 depletion, our results demonstrate the importance of the CREB/CRTC pathway in modulating adipose tissue function.


Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 176 ◽  
Author(s):  
Junhua Yuan ◽  
Qixiao Jiang ◽  
Limin Song ◽  
Yuan Liu ◽  
Manwen Li ◽  
...  

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.


Endocrine ◽  
2020 ◽  
Vol 69 (1) ◽  
pp. 79-91
Author(s):  
Samyra Lopes Buzelle ◽  
Franciele Przygodda ◽  
Rafael Rossi-Valentim ◽  
Graziella Nascimento Ferreira ◽  
Maria Antonieta Rissato Garófalo ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Ines Fki ◽  
Sami Sayadi ◽  
Asma Mahmoudi ◽  
Ines Daoued ◽  
Rim Marrekchi ◽  
...  

Oleuropein and hydroxytyrosol, as major compounds of olive leaves, have been reported to exert numerous pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory activities. The purpose of this study is to evaluate and compare the protective effect of oleuropein- and hydroxytyrosol-rich extracts, derived from olive leaves, on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. In this respect, four groups of male rats (8 per group) were used: control group (Control), group treated with high-fat diet (HFD), group treated with HFD and oleuropein (HFD + OLE), and group treated with HFD and hydroxytyrosol (HFD + HYD). The current research showed that the treatment with the HFD increased the body weight and adipose tissue mass in male rats. Moreover, the plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α were also raised. The hepatic immunohistochemical analysis revealed a significant increase in the expression of inflammatory genes (COX-2, NF-κB, and TNF-α). Equally, it showed a rise of the apoptotic markers (a decrease in the expression of the Bcl-2 and an increase of the P53). In addition, the oral administration of oleuropein- and hydroxytyrosol-rich olive leaf extracts at 16 mg/kg similarly reduced the body weight and adipose tissue mass and improved the lipid profile. Moreover, these extracts, mainly the hydroxytyrosol-rich extract, reduced the elevated liver enzymes, enhanced the antioxidant status, and attenuated the liver inflammation and apoptosis. These findings suggest that the oleuropein- and hydroxytyrosol-rich olive leaf extracts possessed hypolipidemic and hepatoprotective effects against the HFD-induced metabolic disorders by enhancing the antioxidative defense system and blocking the expression of the proteins involved in inflammation and liver damage.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3546
Author(s):  
Kento Mio ◽  
Chiemi Yamanaka ◽  
Tsubasa Matsuoka ◽  
Toshiki Kobayashi ◽  
Seiichiro Aoe

We evaluated whether intake of β-glucan-rich barley flour affects expression levels of genes related to glucose and lipid metabolism in the ileum, liver, and adipose tissues of mice fed a high-fat diet. C57BL/6J male mice were fed a high-fat diet supplemented with high β-glucan barley, for 92 days. We measured the expression levels of genes involved in glucose and lipid metabolism in the ileum, liver, and adipose tissues using DNA microarray and q-PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. The metabolic syndrome indices were improved by barley flour intake. Microarray analysis showed that the expression of genes related to steroid synthesis was consistently decreased in the liver and adipose tissues. The expression of genes involved in glucose metabolism did not change in these organs. In liver, a negative correlation was showed between some SCFAs and the expression levels of mRNA related to lipid synthesis and degradation. Barley flour affects lipid metabolism at the gene expression levels in both liver and adipose tissues. We suggest that SCFAs are associated with changes in the expression levels of genes related to lipid metabolism in the liver and adipose tissues, which affect lipid accumulation.


2006 ◽  
Vol 55 (2) ◽  
pp. 79-89 ◽  
Author(s):  
Kyoichi OSADA ◽  
Makoto FUNAYAMA ◽  
Sayaka FUCHI ◽  
Manabu SAMI ◽  
Yutaka OHTA ◽  
...  

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