scholarly journals Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL/6 J Mice

2019 ◽  
Vol 150 (2) ◽  
pp. 294-302
Author(s):  
Ya-nan Sun ◽  
Jia-qiang Huang ◽  
Zhong-zhou Chen ◽  
Min Du ◽  
Fa-zheng Ren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Protein Degradation ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Serum Glucose ◽  
High Fat

ABSTRACT Background Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear. Objective The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice. Methods Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis. Results Compared with the NFD, the HFD increased (P < 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P < 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis. Conclusions Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.

scholarly journals Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2349-2359 ◽  
Author(s):  
Youli Xi ◽  
Miaozong Wu ◽  
Hongxia Li ◽  
Siqi Dong ◽  
Erfei Luo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Serum Levels ◽  
Whole Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

scholarly journals PHARMACOLOGICAL SCREENING OF ANTI-OBESITY POTENTIAL OF ACORUS CALAMUS LINN. IN HIGH FAT CAFETERIA DIET FED OBESE RATS

2017 ◽  
Vol 10 (4) ◽  
pp. 384 ◽  
Author(s):  
Athesh K ◽  
Joshi G
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
Acorus Calamus ◽  
Dependent Manner ◽  
Fat Pad ◽  
High Fat ◽  
Dose Levels ◽  
Dose Dependent

Objective: To study the anti-obesity potential of aqueous rhizome extract of Acoruscalamus Linn. (AREAC)in high fat diet fed obese rats.Methods: Adult strain male Wistar rats used in this study were fed with High Fat Diet (HFD) for 60 days. For the treatment groups,AREAC was administered in a dose levels of100, 200 and 300 mg/kgbw, orally once a day along with HFD. Rats fed with normal pellet chow were served as normal control. The effect of AREAC on physical parameterssuch as body weight, organ weight, fat pad weights and various biochemical parameterslike serum glucose, insulin, leptin,lipid profile, liver markers, kidney markers and oxidative stress markers were analysed.In-vitro pancreatic lipase inhibition assay of AREAC was also studied.Results: Data of in-vivo studies revealedsignificant (p<0.05) reduction in percentage body weight gain, organ weights, fat pad weights and levels of serum glucose, insulin and leptin after treatment with AREAC in a dose dependent manner. Also, administration of AREAC significantly inhibited the increases in the concentrations of triglycerides, total cholesterol, LDL-cholesterol, VLDL-cholesterol, free-fatty acid and phospholipids in a dose dependent manner whereas, the level of HDL-cholesterol was found to be elevated on treatment. Moreover, on treatment with test drug,the elevated levels of serum liver and kidney markerssuch as AST, ALT, ALP, urea, creatinine were also brought back to near normalcy. Antioxidant status was found to be enhanced in liver tissues after treatment.In-vitro studies showed significant inhibition in the activity of pancreatic lipaseby AREAC.Conclusion: The data of the results obtained clearly depicted that AREAC was found to have pronounced anti-obesity activity particularly at the dose levels of 300 mg/kg bw.Key Words: Obesity, High Fat Diet, Leptin, AcoruscalamusLinn., Orlistat.  

Glucocorticoid aggravates bone micro-architecture deterioration and skeletal muscle atrophy in mice fed on high-fat diet

Steroids ◽  
2019 ◽  
Vol 149 ◽  
pp. 108416 ◽  
Author(s):  
Sulekha Adhikary ◽  
Priyanka Kothari ◽  
Dharmendra Choudhary ◽  
Ashish Kumar Tripathi ◽  
Ritu Trivedi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Skeletal Muscle Atrophy ◽  
High Fat

α-Ionone attenuates high-fat diet-induced skeletal muscle wasting in mice via activation of cAMP signaling

2019 ◽  
Vol 10 (2) ◽  
pp. 1167-1178 ◽  
Author(s):  
Tao Tong ◽  
Minji Kim ◽  
Taesun Park
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Muscle Wasting ◽  
Camp Signaling ◽  
High Fat ◽  
Skeletal Muscle Wasting ◽  
Naturally Occurring ◽  
Flavoring Agent

α-Ionone, a naturally occurring flavoring agent, attenuates muscle atrophy in HFD-fed mice via activation of cAMP signaling.

scholarly journals Magnesium Lithospermate B Attenuates High-Fat Diet-Induced Muscle Atrophy in C57BL/6J Mice

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 104
Author(s):  
Tsun-Li Cheng ◽  
Zi-Yun Lin ◽  
Keng-Ying Liao ◽  
Wei-Chi Huang ◽  
Cian-Fen Jhuo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Skeletal Muscle Atrophy ◽  
Metabolic Abnormalities ◽  
High Fat ◽  
E3 Ligases ◽  
Beneficial Effects ◽  
Magnesium Lithospermate B ◽  
Tnf Α

Magnesium lithospermate B (MLB) is a primary hydrophilic component of Danshen, the dried root of Salvia miltiorrhiza used in traditional medicine, and its beneficial effects on obesity-associated metabolic abnormalities were reported in our previous study. The present study investigated the anti-muscle atrophy potential of MLB in mice with high-fat diet (HFD)-induced obesity. In addition to metabolic abnormalities, the HFD mice had a net loss of skeletal muscle weight and muscle fibers and high levels of muscle-specific ubiquitin E3 ligases, namely the muscle atrophy F-box (MAFbx) and muscle RING finger protein 1 (MuRF-1). MLB supplementation alleviated those health concerns. Parallel changes were revealed in high circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), skeletal TNF receptor I (TNFRI), nuclear factor-kappa light chain enhancer of activated B cells (NF-κB), p65 phosphorylation, and Forkhead box protein O1 (FoxO1) as well as low skeletal phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation. The study revealed that MLB prevented obesity-associated skeletal muscle atrophy, likely through the inhibition of MAFbx/MuRF-1-mediated muscular degradation. The activation of the PI3K-Akt-FoxO1 pathway and inhibition of the TNF-α/TNFRI/NF-κB pathway were assumed to be beneficial effects of MLB.

scholarly journals Resveratrol Ameliorates High-Fat-Diet-Induced Abnormalities in Hepatic Glucose Metabolism in Mice via the AMP-Activated Protein Kinase Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Caiping Lu ◽  
Hanying Xing ◽  
Linquan Yang ◽  
Kaiting Chen ◽  
Linyi Shu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Blood Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Fat ◽  
High Fat ◽  
Amp Activated Protein Kinase

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.

scholarly journals Ganoderma lucidum Extract Reduces Insulin Resistance by Enhancing AMPK Activation in High-Fat Diet-Induced Obese Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3338
Author(s):  
Hyeon A Lee ◽  
Jae-Han Cho ◽  
Qonita Afinanisa ◽  
Gi-Hong An ◽  
Jae-Gu Han ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Ganoderma Lucidum ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Ampk Activation ◽  
High Fat ◽  
Amp Activated Protein Kinase

Ganoderma lucidum is used widely in oriental medicine to treat obesity and metabolic diseases. Bioactive substances extracted from G. lucidum have been shown to ameliorate dyslipidemia, insulin resistance, and type 2 diabetes in mice via multiple 5′ AMP-activated protein kinase (AMPK)-mediated mechanisms; however, further studies are required to elucidate the anti-obesity effects of G. lucidum in vivo. In this study, we demonstrated that 3% G. lucidum extract powder (GEP) can be used to prevent obesity and insulin resistance in a mouse model. C57BL/6 mice were provided with a normal diet (ND) or a high-fat diet (HFD) supplemented with 1, 3, or 5% GEP for 12 weeks and the effect of GEP on body weight, liver, adipose tissue, adipokines, insulin and glucose tolerance (ITT and GTT), glucose uptake, glucose-metabolism related proteins, and lipogenesis related genes was examined. GEP administration was found to reduce weight gain in the liver and fat tissues of the mice. In addition, serum parameters were significantly lower in the 3% and 5% GEP mice groups than in those fed a HFD alone, whereas adiponectin levels were significantly higher. We also observed that GEP improved glucose metabolism, reduced lipid accumulation in the liver, and reduced adipocyte size. These effects may have been mediated by enhanced AMPK activation, which attenuated the transcription and translation of lipogenic genes such as fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), and sterol regulatory element-binding protein-1c (SREBP1c). Moreover, AMP-activated protein kinase (AMPK) activation increased acetyl-CoA carboxylase (ACC), insulin receptor (IR), IR substrate 1 (IRS1), and Akt protein expression and activation, as well as glucose transporter type 1/4 (GLUT1/4) protein production, thereby improving insulin sensitivity and glucose metabolism. Together, these findings demonstrate that G. lucidum may effectively prevent obesity and suppress obesity-induced insulin resistance via AMPK activation.

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