scholarly journals Electroacupuncture Reduces Weight in Diet-Induced Obese Rats via Hypothalamic Tsc1 Promoter Demethylation and Inhibition of the Activity of mTORC1 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jincheng Leng ◽  
Feng Xiong ◽  
Junpeng Yao ◽  
Xiahuan Dai ◽  
Yulei Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Body Fat ◽  
Mammalian Target Of Rapamycin ◽  
Gene Promoter ◽  
Chow Group ◽  
Diet Group ◽  
The Body ◽  
Sprague Dawley ◽  
Tsc1 Gene ◽  
Mtorc1 Signaling

Subject. The study aimed to investigate the mechanism of electroacupuncture reducing weight via tuberous sclerosis complex 1 (Tsc1) promoter methylation, inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. Materials and Methods. Male Sprague-Dawley rats were divided into chow-fed group (chow group) or high-fat diet group (HF group) for 14 weeks. The obesity rats in HF group were randomly divided into electroacupuncture group (EA group) and diet-induced obesity (DIO) group, which received EA stimulation on bilateral ST25, RN12, SP6, and ST36 for 4 weeks or no further treatment, respectively. Methylation of the Tsc1 gene promoter and expression of agouti-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (PoMC) were detected at the 18th week. Results. At week 18, weight, body fat, and the body fat rate in DIO group were significantly higher than those of the chow and EA group. Compared with the chow group, the DIO group had increased methylation of the Tsc1 gene promoter and expression of mTORC1, AgRP, and NPY gene and decreased PoMC in the hypothalamus; after EA, methylation of the Tsc1 gene promoter, mRNA, and protein of the mTORC1 and expression of AgRP and NPY gene decreased and PoMC increased significantly. Conclusions. Our study could shed light on the potential pathway where EA exerts effects on the mechanism of EA treatment for obesity through the hypothalamic Tsc1 promoter demethylation and inhibition of the activity of mTORC1 signaling pathway.

scholarly journals Methylation of Hypothalamic Tsc1-mTOR Signaling in Regulation of Obesity and Obesity Resistance

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yanli Wang ◽  
Sijun Diao ◽  
Maoqing Hu ◽  
Lin Zhang
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Promoter Methylation ◽  
Gene Promoter ◽  
Chow Group ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Expression Levels ◽  
Tsc1 Gene ◽  
Obesity Susceptibility

The Tsc1-mTOR signaling pathway is often related to obesity, and epigenetic modification may lead to expression changes of obesity-related gene. Therefore, we aim to investigate the methylation of the Tsc1-mTOR signaling pathway in regulation of obesity susceptibility. Wistar rats were fed a normal diet or a high-fat diet to develop animal models. Protein and mRNA expression levels of Tsc1-mTOR signaling in the hypothalamus were determined by Western blot and quantitative real-time PCR. Methylation of Tsc1 gene promoter was detected by bisulfite genomic sequence. Both mRNA and protein expression levels of Tsc1 in DIO group hypothalamus were lower; mTOR and its downstream targets S6K1, 4EBP1, and S6 protein expression levels were higher than those of the DIO-R group and the chow group. The Tsc1 gene promoter methylation rate in the hypothalamus was 92.05 ± 3.07 % in the DIO group, 87.27 ± 1.91 % in the DIO-R group, and 88.18 % ± 3.20 % in the chow group, respectively, with significantly higher levels in the DIO group. Both the expression levels of Tsc1 gene promoter methylation and Tsc1-mTOR signaling pathway in the hypothalamus of DIO rats and DIO-R rats are different. These findings may shed light on the potential mechanism for the differentiation of obesity susceptibility.

The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway

2020 ◽  
Vol 156 ◽  
pp. 104798 ◽  
Author(s):  
Ahmad Tamaddoni ◽  
Elahe Mohammadi ◽  
Fatemeh Sedaghat ◽  
Durdi Qujeq ◽  
Atefeh As’Habi
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Anticancer Effects ◽  
Mtorc1 Signaling

Symbiotic effect of lactobacillus acidophilus, Ginger, Pineapple and Green Coffee in the complex management of obesity in rats

2021 ◽  
Vol 30 (1) ◽  
pp. 143-152
Author(s):  
Aml Ghanem ◽  
Osama M. Abonama ◽  
Ahmed I. Abd El Maksoud ◽  
Mokhtar M. El-Zawahry ◽  
Dalia Elebeedy
Keyword(s):  
Body Fat ◽  
Lactobacillus Acidophilus ◽  
Biochemical Parameters ◽  
Histopathological Examination ◽  
Positive Control ◽  
Feed Additives ◽  
The Body ◽  
Control Group ◽  
Green Coffee ◽  
Sprague Dawley

Background: Obesity is a chronic metabolic disease associated with having excess body fat that could be influenced by many factors. Our study aimed to assess the powerful effect of Lactobacillus acidophilus alone or combined (symbiotic) with Prebiotic such as Ginger, Pineapple and Green Coffee as anti-obesity agents. Methodology: Using 8 groups (10 rats each) of Sprague-Dawley rats, Group 1 was kept as a negative control, Group 2 positive control, while other groups were orally given Lactobacillus acidophilus, Ginger, Pineapple and Green Coffee individually and in combination with Probiotics, for 45 days till the end of the experiment while the body weight of rats was recorded.Blood samples were collected for biochemical parameters analysis and organs were dissected and homogenized to analyze obesity-related biomarkers, Results: Our results revealed that either individual or mixed administration of this pro and prebiotics decreased the body and organs, specifically those treated with the mixture or probiotic and prebiotic, also serum (HDL), CAT), and (SOD) was decreased (P <0.05), while other biochemical parameters (T.G), (CHOL), (U.A), (Creat), Urea, (GOT),(GPT) and (ALP); ( significantly (P<0.05) was decreased when compared with the positive control group, Nevertheless, the histopathological examination showed the reduction of adipose tissue in kidney, liver, and Pancreas showed overestimate reductions in the percentage of body fat. Conclusions: This study showed a promising effect of Lactobacillus acidophilus when it combined with these plants as natural feed additives on obesity.

scholarly journals Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

2021 ◽  
Vol 10 (19) ◽  
pp. 4362
Author(s):  
Ronald Peek ◽  
Lotte L. Eijkenboom ◽  
Didi D. M. Braat ◽  
Catharina C. M. Beerendonk
Keyword(s):  
Signaling Pathway ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Autologous Transplantation ◽  
Mammalian Target Of Rapamycin ◽  
Short Term ◽  
Ovarian Cortex ◽  
Short Term Exposure ◽  
Mtorc1 Signaling ◽  
Restoration Of Fertility

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing’s sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

Leptin inhibits insulin binding in isolated rat adipocytes

1997 ◽  
Vol 155 (3) ◽  
pp. R5-R7 ◽  
Author(s):  
K Walder ◽  
A Filippis ◽  
S Clark ◽  
P Zimmet ◽  
GR Collier
Keyword(s):  
Insulin Resistance ◽  
Body Fat ◽  
Insulin Binding ◽  
The Body ◽  
Displacement Curve ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Binding Data ◽  
Isolated Adipocytes ◽  
Dose Dependent

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.

scholarly journals Role of BDNF-mTORC1 Signaling Pathway in Female Depression

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xianquan An ◽  
Xiaoxiao Yao ◽  
Bingjin Li ◽  
Wei Yang ◽  
Ranji Cui ◽  
...  
Keyword(s):  
Public Health ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Public Health Problem ◽  
Low Mood ◽  
Mtorc1 Signaling ◽  
Prevention And Treatment ◽  
Close Relationship ◽  
The Brain

Depression is a common psychological and mental disorder, characterized by low mood, slow thinking and low will, and even suicidal tendencies in severe cases. It imposes a huge mental and economic burden on patients and their families, and its prevention and treatment have become an urgent public health problem. It is worth noting that there is a significant gender difference in the incidence of depression. Studies have shown that females are far more likely to suffer from depression than males, confirming a close relationship between estrogen and the onset of depression. Moreover, recent studies suggest that the brain-derived neurotrophic factor- (BDNF-) mammalian target of rapamycin complex-1 (mTORC1) signaling pathway is a crucial target pathway for improving depression and mediates the rapid antidepressant-like effects of various antidepressants. However, it is not clear whether the BDNF-mTORC1 signaling pathway mediates the regulation of female depression and how to regulate female depression. Hence, we focused on the modulation of estrogen-BDNF-mTORC1 signaling in depression and its possible mechanisms in recent years.

Tanshinone IIA Regulates Osteoblast Differentiation and Promotes Fracture Healing via Mammalian Target of Rapamycin Complex 1 Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1737-1743
Author(s):  
Ming Fang ◽  
Xingwu Wang ◽  
Yongli Wei ◽  
Wuliang Yu ◽  
Jianmeng Lu
Keyword(s):  
Fracture Healing ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Callus Formation ◽  
Mammalian Target Of Rapamycin ◽  
Tanshinone Iia ◽  
Control Group ◽  
Osteoblast Proliferation ◽  
Mice Model ◽  
Mtorc1 Signaling

This study assessed the effect and potential molecular mechanism of tanshinone IIA on fracture healing. Mice model with fracture were established. Digital radiographic photographic system was used to detect callus formation after treatment with tanshinone II A (Tan IIA) and alkaline phosphatase (ALP) staining analyzed ALP activity. Osteoblast proliferation was also measured. Western blot and Quantitative real-time PCR (qRT-PCR) measured osteogenic markers expression. Compared with control group, Tan IIA treatment could increase callus formation, stimulate osteoblast proliferation, osteogenic proteins and genes expression, and activate mTORC1 signaling pathway. However, Tan IIA’s effects were significantly inhibited after rapamycin treatment. Tan IIA regulates osteoblast differentiation by mTORC1 signaling and promotes intramembranous ossification in the process of callus formation, which accelerates bone healing.

scholarly journals Proteomics of autism and Alzheimer’s mouse models reveal common alterations in mTOR signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mencer ◽  
Maryam Kartawy ◽  
Felix Lendenfeld ◽  
Huda Soluh ◽  
Manish Kumar Tripathi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mouse Models ◽  
Neurological Disorders ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Autism Spectrum ◽  
Novel Therapy ◽  
Western Blots ◽  
Mtorc1 Signaling

AbstractAutism spectrum disorder (ASD) and Alzheimer’s disease (AD) are two different neurological disorders that share common clinical features, such as language impairment, executive functions, and motor problems. A genetic convergence has been proposed as well. However, the molecular mechanisms of these pathologies are still not well understood. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions. Previously, we have shown that NO and SNO are involved in the InsG3680(+/+) ASD and P301S AD mouse models. Here, we performed large-scale computational biology analysis of the SNO-proteome followed by biochemical validation to decipher the shared mechanisms between the pathologies. This analysis pointed to the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway as one of the shared molecular mechanisms. Activation of mTOR in the cortex of both mouse models was confirmed by western blots that showed increased phosphorylation of RPS6, a major substrate of mTORC1. Other molecular alterations affected by SNO and shared between the two mouse models, such as synaptic-associated processes, PKA signaling, and cytoskeleton-related processes were also detected. This is the first study to decipher the SNO-related shared mechanisms between SHANK3 and MAPT mutations. Understanding the involvement of SNO in neurological disorders and its intersection between ASD and AD might help developing an effective novel therapy for both neuropathologies.

scholarly journals Association between different types of plant-based diets and leptin levels in healthy volunteers

2019 ◽  
Author(s):  
Patrycja Gogga ◽  
Aleksandra Śliwińska ◽  
Ewa Aleksandrowicz-Wrona ◽  
Syliwa Małgorzewicz
Keyword(s):  
Fatty Acids ◽  
Body Fat ◽  
Diet Group ◽  
The Body ◽  
Vegan Diet ◽  
Omega 3 ◽  
Dietary Recall ◽  
Total Carbohydrates ◽  
Total Fat ◽  
Plasma Leptin

Leptin is an important factor regulating appetite and energety metabolism; disturbances in its signaling are related to adiposity and contribute to the excessive body fat. About a third of the human population is overweight or suffers from obesity, as well as from associated medical conditions. It is well established that vegetarian, especially vegan, diet is very effective in lowering BMI and body fat, thus, plant-based diets are associated with a lower risk of obesity. The aim of this study was to evaluate the plasma levels of leptin in lacto-ovo-vegetarian and vegan volunteers with normal BMI. The intake of energy and selected diet components such as polyunsaturated fatty acids (PUFA) and carbohydrates was also investigated. The study involved healthy women – 14 omnivores, 17 lacto-ovo-vegetarians, and 11 vegans. All women had a normal BMI (18.5-24.99). The plasma leptin levels were examined with immunoenzymatic test (ELISA). All participants were interviewed to estimate their nutrient intake by performing a 24-hour dietary recall. Both lacto-ovo-vegetarians and vegans had lower plasma leptin concentrations than their meat-consuming counterparts. Every analyzed diet group had a different body fat content, with the highest level in omnivores and the lowest in vegans. All participants had similar calorie, total fat, and total carbohydrates intake. Total PUFA and specifically omega-3 fatty acids consumption was lower in omnivores when compared to both types of plant diet; the same was found for fiber intake. Our results suggest that adopting a plant-based diet may be beneficial for energetic metabolism, as it significantly lowers the body fat storage and circulating leptin levels.

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