scholarly journals 2-Bromo-4′-methoxychalcone and 2-Iodo-4′-methoxychalcone Prevent Progression of Hyperglycemia and Obesity via 5′-Adenosine-Monophosphate-Activated Protein Kinase in Diet-Induced Obese Mice

2018 ◽  
Vol 19 (9) ◽  
pp. 2763 ◽  
Author(s):  
Chi-Ting Hsieh ◽  
Fang-Rong Chang ◽  
Yi-Hong Tsai ◽  
Yang-Chang Wu ◽  
Tusty-Jiuan Hsieh
Keyword(s):  
Protein Kinase ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Glucose Consumption ◽  
Adenosine Monophosphate ◽  
Lead Compounds ◽  
New Class ◽  
Obesity And Diabetes ◽  
Skeletal Myotubes ◽  
Cellular Lipid Accumulation

Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

scholarly journals Formononetin, an isoflavone, activates AMP-activated protein kinase/β-catenin signalling to inhibit adipogenesis and rescues C57BL/6 mice from high-fat diet-induced obesity and bone loss

2017 ◽  
Vol 117 (5) ◽  
pp. 645-661 ◽  
Author(s):  
Jyoti Gautam ◽  
Vikram Khedgikar ◽  
Priyanka Kushwaha ◽  
Dharmendra Choudhary ◽  
Geet Kumar Nagar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bone Loss ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Binding Protein ◽  
Regulatory Element ◽  
Adipogenic Differentiation ◽  
High Fat ◽  
Amp Activated Protein Kinase

AbstractBalance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of β-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT’s rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/β-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.

Loss of CREB coactivator CRTC1 in SF1 cells leads to hyperphagia and obesity by high-fat diet but not normal chow diet

Endocrinology ◽  
2021 ◽  
Author(s):  
Shigenobu Matsumura ◽  
Fuka Ishikawa ◽  
Tsutomu Sasaki ◽  
Mike Krogh Terkelsen ◽  
Kim Ravnskjaer ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Body Weight Gain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Ventromedial Hypothalamus ◽  
Whole Body ◽  
Appetite Regulation ◽  
High Fat ◽  
Normal Chow ◽  
The Brain

Abstract Cyclic adenosine monophosphate responsive element–binding protein-1 (CREB1)-regulated transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that translocates to the nucleus in response to cyclic adenosine monophosphate. Whole-body knockdown of Crtc1 causes obesity, resulting in increased food intake and reduced energy expenditure. CRTC1 is highly expressed in the brain; therefore, it might play an important role in energy metabolism via the neuronal pathway. However, the precise mechanism by which CRTC1 regulates energy metabolism remains unknown. Here, we showed that mice lacking CRTC1, specifically in steroidogenic factor-1 expressing cells (SF1 cells), were sensitive to high-fat diet (HFD)-induced obesity, exhibiting hyperphagia and increased body weight gain. The loss of CRTC1 in SF1 cells impaired glucose metabolism. Unlike whole-body CRTC1 knockout mice, SF1 cell-specific CRTC1 deletion did not affect body weight gain or food intake in normal chow feeding. Thus, CRTC1 in SF1 cells is required for normal appetite regulation in HFD-fed mice. CRTC1 is primarily expressed in the brain. Within hypothalamus which plays an important role for appetite regulation, SF1 cells are only found in ventromedial hypothalamus. RNA sequencing analysis of micro-dissected ventromedial hypothalamus samples revealed that the loss of CRTC1 significantly changed the expression levels of certain genes. Our results revealed the important protective role of CRTC1 in SF1 cells against dietary metabolic imbalance.

Green tea catechins attenuate high-fat diet effects related to obesity and diabetes without effect hypothalamic expression of TLR4 pathway or serotoninergic 1B and 2C receptors

2013 ◽  
Author(s):  
Marcos Hiromu Okuda ◽  
de Santana Aline Alves ◽  
Mayara Franzoi Moreno ◽  
Ana Claudia Hachul ◽  
Nelson Inacio Neto ◽  
...  
Keyword(s):  
Green Tea ◽  
High Fat Diet ◽  
High Fat ◽  
Tea Catechins ◽  
Green Tea Catechins ◽  
Obesity And Diabetes

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

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