scholarly journals Jianpi Qinghua Formula Reduced Intramyocellular Lipids (IMCLs) by Inhibiting Excessive Activation of mTORC1

2021 ◽  
Author(s):  
Xv Han ◽  
Qingguang Chen ◽  
Yahua Liu ◽  
Junfei Xv ◽  
Hao Lu
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
High Fat Diet ◽  
C2c12 Cells ◽  
Akt Pathway ◽  
High Fat ◽  
Akt Phosphorylation

Abstract Background:IMCLs are an important factor in skeletal muscle insulin resistance. This study aimed to explore the effect of Jianpi Qinghua formula (JPQHF) on IMCLs and its mechanism, as well as the relationship between IMCLs and other skeletal muscle insulin sensitivity factors, thereby elucidating the mechanism by which JPQHF improves insulin sensitivity.Methods: In an in vivo experiment, JPQHF and pioglitazone (PIO) were individually used to treat C57 mice with high-fat diet-induced obesity. In an in vitro experiment, JPQHF and rapamycin in serum were individually used to treat C2C12 cells induced with palmitic acid. The IMCLs of tissue and cells were subjected to oil red O staining. The RNA and protein expression of PPARγ, myogenin, mTORC1 and members of the PI3K/AKT pathway in skeletal muscle tissue and C2C12 cells was examined. Differences between the different intervention groups were determined.Results: IMCLs were significantly increased in mice with obesity induced by a high-fat diet and the C2C12 cell line treated with palmitic acid compared to the corresponding controls. mTORC1 phosphorylation and PPARγ levels were also increased, and AKT phosphorylation and myogenin levels were decreased. Intervention with JPQHF reversed the above changes. In addition, the PPARγ level in C2C12 cells was reduced after intervention with rapamycin, an inhibitor of mTORC1. However, AKT phosphorylation and myogenin levels did not recover after rapamycin intervention.Conclusion: IMCLs were significantly increased in obese C57 mice and palmitic acid-treated C2C12 cells. JPQHF reduced IMCLs both in vivo and in vitro. Mechanistically, this effect likely occurred through JPQHF-mediated inhibition of the overactivation of mTORC1 and a subsequent reduction in the expression of PPARγ. However, the function of JPQHF in elevating myogenin levels and the PI3K/AKT pathway may not be entirely dependent on mTORC1.

scholarly journals Effect of Dietary Silk Peptide on Obesity, Hyperglycemia, and Skeletal Muscle Regeneration in High-Fat Diet-Fed Mice

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 377 ◽  
Author(s):  
Kippeum Lee ◽  
Heegu Jin ◽  
Sungwoo Chei ◽  
Hyun-Ji Oh ◽  
Jeong-Yong Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Skeletal Muscle Regeneration ◽  
High Fat ◽  
Skeletal Muscle Function ◽  
Silk Peptide

Obesity is associated with excess body fat accumulation that can cause hyperglycemia and reduce skeletal muscle function and strength, which characterize the development of sarcopenic obesity. In this study, we aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet (HFD)-induced obesity and whether it regulates glucose uptake and muscle differentiation using in vivo and in vitro approaches. Our findings demonstrate that SP inhibits body mass gain and the expression of adipogenic transcription factors in visceral adipose tissue (VAT). SP also had an anti-diabetic effect in VAT and skeletal muscle because it upregulated glucose transporter type 4 (GLUT4) and uncoupling protein 3 (UCP3) expression. Furthermore, SP reduced ubiquitin proteasome and promoted myoblast determination protein 1 (MyoD)/myogenic factor 4 (myogenin) expression, implying that it may have potential for the treatment of obesity-induced hyperglycemia and obesity-associated sarcopenia.

scholarly journals Enteric Neuropathy Can Be Induced by High Fat Diet In Vivo and Palmitic Acid Exposure In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81413 ◽  
Author(s):  
Ulrikke Voss ◽  
Elin Sand ◽  
Björn Olde ◽  
Eva Ekblad
Keyword(s):  
Palmitic Acid ◽  
High Fat Diet ◽  
Acid Exposure ◽  
High Fat ◽  
Enteric Neuropathy

scholarly journals Endothelial NOX5 Expression Modulates Thermogenesis and Lipolysis in Mice Fed with a High-Fat Diet and 3T3-L1 Adipocytes through an Interleukin-6 Dependent Mechanism

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Jorge G. García ◽  
Carlos de Miguel ◽  
Fermín I. Milagro ◽  
Guillermo Zalba ◽  
Eduardo Ansorena
Keyword(s):  
Adipose Tissue ◽  
Palmitic Acid ◽  
High Fat Diet ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Conditioned Media ◽  
In Vivo Model ◽  
High Fat ◽  
Previously Treated

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present work is to describe the effect of endothelial NOX5 expression on neighboring adipose tissue in obesity conditions by using two systems. An in vivo model based on NOX5 conditional knock-in mice fed with a high-fat diet and an in vitro model developed with 3T3-L1 adipocytes cultured with conditioned media of endothelial NOX5-expressing bEnd.3 cells, previously treated with glucose and palmitic acid. Endothelial NOX5 expression promoted the expression and activation of specific markers of thermogenesis and lipolysis in the mesenteric and epididymal fat of those mice fed with a high-fat diet. Additionally, the activation of these processes was derived from an increase in IL-6 production as a result of NOX5 activity. Accordingly, 3T3-L1 adipocytes treated with conditioned media of endothelial NOX5-expressing cells, presented higher expression of thermogenic and lipolytic genes. Moreover, endothelial NOX5-expressing bEnd.3 cells previously treated with glucose and palmitic acid also showed interleukin (IL-6) production. Finally, it seems that the increase in IL-6 stimulated the activation of markers of thermogenesis and lipolysis through phosphorylation of STAT3 and AMPK, respectively. In conclusion, in response to obesogenic conditions, endothelial NOX5 activity could promote thermogenesis and lipolysis in the adipose tissue by regulating IL-6 production.

scholarly journals Inhibiting myeloperoxidase prevents onset and reverses established high-fat diet-induced microvascular insulin resistance

2019 ◽  
Vol 317 (6) ◽  
pp. E1063-E1069 ◽  
Author(s):  
Weidong Chai ◽  
Kevin Aylor ◽  
Zhenqi Liu ◽  
Li-Ming Gan ◽  
Erik Michaëlsson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Disease Risk ◽  
Therapeutic Potential ◽  
Cardiovascular Disease Risk ◽  
Sprague Dawley ◽  
High Fat

A high-fat diet (HFD) can rapidly recruit neutrophils to insulin target tissues and within days induce microvascular insulin resistance (IR). Myeloperoxidase (MPO) is highly enriched in neutrophils, can inhibit nitric oxide-mediated vasorelaxation in vitro and is associated with increased cardiovascular disease risk. AZD5904 irreversibly inhibits MPO and in human clinical trials. MPO knockout, or chemical inhibition, blunts HFD-induced metabolic IR in mice. Whether MPO affects microvascular IR or muscle metabolic insulin sensitivity in vivo is unknown. We used contrast-enhanced ultrasound and the euglycemic insulin clamp to test whether inhibiting MPO could prevent the development or reverse established HFD-induced metabolic and/or microvascular IR in Sprague-Dawley rats. Two weeks of HFD feeding blocked insulin-mediated skeletal muscle capillary recruitment, inhibited glucose utilization, and insulin signaling to muscle. Continuous subcutaneous AZD5904 infusion during the 2 wk selectively blocked HFD’s microvascular effect. Furthermore, AZD5904 infusion during the last 2 of 4 wk of HFD feeding restored microvascular insulin sensitivity but not metabolic IR. We conclude that inhibiting MPO selectively improves vascular IR. This selective microvascular effect may connote a therapeutic potential for MPO inhibition in the prevention of vascular disease/dysfunction seen in IR humans.

scholarly journals Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Alice C. Rodrigues ◽  
Alexandre R. Spagnol ◽  
Flávia de Toledo Frias ◽  
Mariana de Mendonça ◽  
Hygor N. Araújo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Insulin Sensitivity ◽  
Mitochondrial Respiration ◽  
High Fat Diet ◽  
C2c12 Cells ◽  
High Fat ◽  
Spare Capacity

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

scholarly journals Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

2017 ◽  
Vol 43 (5) ◽  
pp. 1961-1973 ◽  
Author(s):  
Yan Bai ◽  
Zhenli Su ◽  
Hanqi Sun ◽  
Wei Zhao ◽  
Xue Chen ◽  
...  
Keyword(s):  
Action Potential ◽  
Protein Expression ◽  
High Fat Diet ◽  
Qt Prolongation ◽  
Electrical Remodeling ◽  
High Fat ◽  
Treatment Groups ◽  
Aloe Emodin

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

scholarly journals High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Gu ◽  
Chong Liu ◽  
TianYe Yang ◽  
Ming Zhan ◽  
Zhikang Cai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Benign Prostatic Hyperplasia ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Prostatic Hyperplasia ◽  
Prostate Tissue ◽  
High Fat ◽  
Ghrelin Receptor

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

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