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.

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

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 CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice

2019 ◽  
Vol 317 (6) ◽  
pp. E973-E983 ◽  
Author(s):  
Annie Hasib ◽  
Chandani K. Hennayake ◽  
Deanna P. Bracy ◽  
Aimée R. Bugler-Lamb ◽  
Louise Lantier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
High Fat Diet ◽  
Critical Role ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.

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 Z-ajoene from Crushed Garlic Alleviates Cancer-Induced Skeletal Muscle Atrophy

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2724 ◽  
Author(s):  
Hyejin Lee ◽  
Ji-Won Heo ◽  
A-Reum Kim ◽  
Minson Kweon ◽  
Sorim Nam ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Inflammatory Responses ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Janus Kinase ◽  
Skeletal Muscle Atrophy ◽  
E3 Ligases

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world’s most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

scholarly journals Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2274
Author(s):  
Roi Cal ◽  
Heidi Davis ◽  
Alish Kerr ◽  
Audrey Wall ◽  
Brendan Molloy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Murine Model ◽  
The Body ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Disuse Atrophy ◽  
Tnf Α

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

scholarly journals PO-094 p38 MAPK controls of E3-ligases expression and soleus atrophy attenuation in rat upon hindlimb unloading

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Tatiana Nemirovskaya ◽  
Svetlana Belova ◽  
Boris Shenkman ◽  
Ekaterina Mochalova
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
P38 Mapk ◽  
Muscle Atrophy ◽  
Mapk Signaling ◽  
Hindlimb Unloading ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
Control Group ◽  
E3 Ligases

Objective Unloading causes rapid skeletal muscle atrophy mainly due to the increased protein degradation. Muscle proteolysis results from the activation of ubiquitin-proteasome systems. The ubiquitination proteins are carried out by muscle-specific E3 ubiquitin ligases – MuRF-1 and MAFbx. It is known that MuRF-1 and MAFbx expression significantly increases on the third day of muscle unloading. We tested the hypothesis that p38 MAPK participates in the regulation of E3 ligases expression and the development of skeletal muscle atrophy during unloading. To check this idea we inhibited p38 MAPK by VX-745. Methods 21 male Wistar rats were divided into 3 groups (7 rats in each group): intact control (C), rats suspended for 3 days (HS) and rats suspended and injected i.p. with VX-745 (10 mg/kg/day) (VX). The hindlimb suspension was carried out according to Morey-Holton technique. The animals were anaesthetised with an i.p. injection of tribromoethanol (240 mg/kg). Under anesthesia, the m.soleus were excised, frozen in liquid nitrogen, and stored at -80°C until further analysis. All procedures with the animals were approved by the Biomedicine Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences/Physiology section of the Russian Bioethics Committee. The statistical analysis was performed using the REST 2009 v.2.0.12 and Origin Pro programs at the significance level set at 0,05. The results are given as median in percent and interquartile range (0.25-0.75). Results The muscle weight in HS group was significantly reduced (72,3±2,5 mg) compared to C (83,0±3 mg), p<0.05, while the soleus weight of VX group didn’t differ from the control (84.2±5 mg). The MuRF1 mRNA expression was elevated dramatically in HS group (165 (138-210) %) when compared with the control (100 (64.6-112.5) %), p<0.05.  In the VX group the level of MuRF1 mRNA expression (127 (105-138) %) didn’t differ from the control group. The MAFbx mRNA expression was observed to increase equally in both suspended groups (294 (265-342) % and (271 (239-309) %).) vs C (100 (91-106) %) so, VX-745 administration did not have any significant effect on its expression. We also found that the level of ubiquitin mRNA expression in the soleus of HS rats was higher (423 (325-485) %) in comparison with the C group (100 (78-166) %, p<0.05) while VX-745 injection prevented increasing the  mRNA ubiquitin expression (200 (190-237) %). We discovered that the elevation of calpain-1 mRNA expression upon HS was prevented by VX-745 administration and its level didn’t differ from the control group (C - 100 (97-105) %, HS – 120 (116-133) %, VX - 107 (100-115) %, p<0.05). Conclusions Thus, the results indicate that the p38 MAPK signaling pathway takes part in the regulation of E3-ligase MuRF1 but not MAFbx expression. The p38 MAPK inhibition prevents muscle atrophy and the elevation of ubiquitin and calpain mRNA expression at the early stage of hindlimb unloading. This work was supported by RFBR grant No.17-04-01838.

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