scholarly journals Activation of the adipocyte CREB/CRTC pathway in obesity

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.

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 ◽  
...  

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

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Samyra Buzelle ◽  
Graziella Ferreira‐Sodré ◽  
Rafael Valentim ◽  
Franciele Przygodda ◽  
Maria Antonieta Garófalo ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 920-920
Author(s):  
Sanjay Pandey Diksha Joshi ◽  
Saurabh Singh ◽  
Sushma Ray ◽  
Anant Narayan Bhatt ◽  
K Natarajan ◽  
...  

Abstract Obesity is a major risk factor for type 2 diabetes, NAFLD, chronic diseases and cancer. Insulin resistance, oxidative stress, high ectopic lipid levels and meta-inflammation are the mechanisms proposed to play a leading role in the morbidity associated with obesity. Energy restriction mimetics (ERMAs) has also been shown earlier to reduce the scale and the severity of these disorders by mimicking the physiological effects of the Energy Restriction. In present study we propose that the use of 2-DG as ERMA can be effective in regulating the High Fat Diet (HFD) induced obesity. Effect of 2-DG (0.4% w/v in drinking water) on the HFD and Insulin Resistance (IR). HFD induced change in body weight, adipose tissue mass, and ectopic lipid levels was assessed as the measure of obesity.IR and glucose levels were also estimated to evaluate the effect of 2-DG on the insulin sensitivity in HFD mice. 2-DG significantly altered HFD induced increase in the mice body weight, epididymal White Adipose Tissue (WAT) and liver weight. 2-DG fed mice also showed reduced lipid levels in serum and liver. Furthermore, 2-DG also reduced the oxidative damage in the liver with concomitant increase in enzymatic (SOD and Catalase) and non-enzymatic (reduced Glutathione) antioxidant levels. 2-DG fed mice also showed reduced levels of Leptin, IL-6 and TGF-β which are early drivers of the etiology of the metabolic diseases. Our results suggest that 2-DG as ERMA can prevent obesity and etiology of associated disorders. However, more relevant models are needed to further strengthen these observation


PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e40351 ◽  
Author(s):  
Stéphanie Lucas ◽  
Solenne Taront ◽  
Christophe Magnan ◽  
Laurence Fauconnier ◽  
Myriam Delacre ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document