Mitochondrial dysfunction and inhibition of myoblast differentiation in mice with high‐fat‐diet‐induced pre‐diabetes

Xu, Dengqiu; Jiang, Zhenzhou; Sun, Zeren; Wang, Lu; Zhao, Guolin; Hassan, Hozeifa Mohamed; Fan, Sisi; Wang, Zhou; Han, Shuangshuang; Zhang, Luyong; Wang, Tao

doi:10.1002/jcp.27512

Cited by 36 publications

(36 citation statements)

References 52 publications

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“…In general, a fat energy composition of up to 50-60% is observed in a high fat diet mouse model. Most researchers use these values to establish an obesity model [33] or a diabetic model [34]. According to Catta-Preta et al [23], in a 60% fat energy diet (lard, olive oil, SFO, and canola oil separately), only lard contributes to fat mass (10% fat energy); In our study, mice were supplied with 35% fat energy are consistent with this report.…”

Section: Discussionsupporting

confidence: 90%

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications

et al. 2020

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Background: The traditional Chinese diet blends lard with vegetable oil, keeping the fatty acid balance intake ratio of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids at nearly 1:1:1. However, the effects of a mixture of lard and vegetable oil on lipid metabolism have never been researched. In the present study, by simulating Chinese high-fat dietary habits, we explored the effects of a mixture of lard and vegetable oil on lipid metabolism. Methods: We randomly assigned 50 male C57BL/6 J mice to 5 groups (10 in each group) and fed them lard, sunflower oil (SFO), soybean oil (SBO), lard blended with sunflower oil (L-SFO), or lard blended with soybean oil (L-SBO) for 12 weeks. Results: We found that the final body weights of mice in the lard group were significantly higher than those of mice in the SFO and SBO groups. Body fat rate and volume of fat cell of the lard group were significantly higher than those of the SFO, SBO, and L-SBO groups. Liver triglyceride level of the lard group increased significantly compared to the other groups. Although body fat rate and liver triglyceride level in the SBO and SFO groups decreased compared to those in the other groups, the high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ratio were also significantly decreased in the SBO and SFO groups. Conclusions: We found that a lard diet induced accumulation of body fat, liver and serum lipids, which can increase the risk of obesity, non-alcoholic fatty acid liver disease, and atherosclerosis. The vegetable oil diet resulted in cholesterol metabolism disorders even though it did not lead to obesity. The mixed oil diet induced body fat accumulation, but did not cause lipid accumulation in the liver and serum. Thus, differential oil/fat diets have an impact on differential aspects in mouse lipid metabolism.

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Section: Discussionsupporting

confidence: 90%

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications

et al. 2020

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“…Serum glucose concentrations were determined using a glucometer at 0, 30, 60, and 120 min after insulin injection. The areas under the curves (AUCs) of the insulin tolerance test results were calculated [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…Mitochondrial dysfunction may affect energy production, thereby impairing cell function, and has been implicated in many acute and chronic diseases [ 5 – 7 ]. A strong association of insulin resistance and T2DM development with mitochondrial dysfunction is evident, and mitochondrial dysfunction causes insulin resistance [ 8 – 10 ]. However, the details of this association remain unclear.…”

Section: Introductionmentioning

confidence: 99%

The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis

Jiang

et al. 2020

Acta Pharmacol Sin

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Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg −1 ·d −1 ) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes.

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“…Western blot analysis was performed as described previously. 20 In brief, protein extracts were fractionated on 6-12% sodium dodecyl sulphate polyacrylamide gels and transferred onto polyvinylidene fluoride membranes (Millipore, Billerica, MA, USA) via electroblotting. The membranes were blocked in Tris-buffered saline containing 5% bovine serum albumin for 90 min at room temperature.…”

Section: Western Blot Analysismentioning

confidence: 99%

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

Zhao

Jiang

et al. 2020

J cachexia sarcopenia muscle

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Background Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the loss of dystrophin, which results in inflammation, fibrosis, and the inhibition of myoblast differentiation in skeletal muscle. Catalpol, an iridoid glycoside, improves skeletal muscle function by enhancing myogenesis; it has potential to treat DMD. We demonstrate the positive effects of catalpol in dystrophic skeletal muscle. Methods mdx (loss of dystrophin) mice (n = 18 per group) were treated with catalpol (200 mg/kg) for six consecutive weeks. Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Molecular docking and ligand-target interactions, RNA interference, immunofluorescence, and plasmids transfection were utilized to explore the protective mechanism in DMD by which catalpol binding with transforming growth factor-βactivated kinase 1 (TAK1) in skeletal muscle. Results Six weeks of catalpol treatment improved whole-body muscle health in mdx mice, which was characterized by reduced plasma creatine kinase (n = 18, À35.1%, P < 0.05) and lactic dehydrogenase (n = 18, À10.3%, P < 0.05) activity. These effects were accompanied by enhanced grip strength (n = 18, +25.4%, P < 0.05) and reduced fibrosis (n = 18, À29.0% for hydroxyproline content, P < 0.05). Moreover, catalpol treatment protected against muscle fatigue and promoted muscle recovery in the tibialis anterior (TA) and diaphragm (DIA) muscles (n = 6, +69.8%, P < 0.05 and + 74.8%, P < 0.001, respectively), which was accompanied by enhanced differentiation in primary myoblasts from DMD patients (n = 6, male, mean age: 4.7 ± 1.9 years) and mdx mice. In addition, catalpol eliminated p-TAK1 overexpression in mdx mice (n = 12, À21.3%, P < 0.05) and primary myoblasts. The catalpol-induced reduction in fibrosis and increased myoblast differentiation resulted from the inhibition of TAK1 phosphorylation, leading to reduced myoblast trans-differentiation into myofibroblasts. Catalpol inhibited the phosphorylation of TAK1 by binding to TAK1, possibly at Asp-206, Thr-208, Asn-211, Glu-297, Lys-294, and Tyr-293. Conclusions Our findings show that catalpol and TAK1 inhibitors substantially improve whole-body muscle health and the function of dystrophic skeletal muscles and may provide a novel therapy for DMD.

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Mitochondrial dysfunction and inhibition of myoblast differentiation in mice with high‐fat‐diet‐induced pre‐diabetes

Cited by 36 publications

References 52 publications

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications

The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis

A potential therapeutic effect of catalpol in Duchenne muscular dystrophy revealed by binding with TAK1

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