Caloric Restriction Followed by High Fat Feeding Predisposes to Oxidative Stress in Skeletal Muscle Mitochondria

Diabetes mellitus is a systemic metabolic disorder associated with mitochondrial dysfunction, with mitochondrial permeability transition (MPT) pore opening being recognized as one of its pathogenic mechanisms. Alisporivir has been recently identified as a non-immunosuppressive analogue of the MPT pore blocker cyclosporin A and has broad therapeutic potential. The purpose of the present work was to study the effect of alisporivir (2.5 mg/kg/day i.p.) on the ultrastructure and functions of the skeletal muscle mitochondria of mice with diabetes mellitus induced by a high-fat diet combined with streptozotocin injections. The glucose tolerance tests indicated that alisporivir increased the rate of glucose utilization in diabetic mice. An electron microscopy analysis showed that alisporivir prevented diabetes-induced changes in the ultrastructure and content of the mitochondria in myocytes. In diabetes, the ADP-stimulated respiration, respiratory control, and ADP/O ratios and the level of ATP synthase in the mitochondria decreased, whereas alisporivir treatment restored these indicators. Alisporivir eliminated diabetes-induced increases in mitochondrial lipid peroxidation products. Diabetic mice showed decreased mRNA levels of Atp5f1a, Ant1, and Ppif and increased levels of Ant2 in the skeletal muscles. The skeletal muscle mitochondria of diabetic animals were sensitized to the MPT pore opening. Alisporivir normalized the expression level of Ant2 and mitochondrial susceptibility to the MPT pore opening. In parallel, the levels of Mfn2 and Drp1 also returned to control values, suggesting a normalization of mitochondrial dynamics. These findings suggest that the targeting of the MPT pore opening by alisporivir is a therapeutic approach to prevent the development of mitochondrial dysfunction and associated oxidative stress in the skeletal muscles in diabetes.

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Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2015-0070 ◽

2016 ◽

Vol 13 (2) ◽

Cited By ~ 16

Author(s):

Nachimuthu Maithilikarpagaselvi ◽

Magadi Gopalakrishna Sridhar ◽

Rathinam Palamalai Swaminathan ◽

Ramalingam Sripradha

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Body Weight ◽

Density Lipoprotein ◽

High Fat ◽

Oxidative Stress Parameters ◽

Tnf Α ◽

Male Wistar Rats ◽

Fat Feeding

Abstract: The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats.: Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment.: High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition.: Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.

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3,5-Diiodo-L-Thyronine Affects Structural and Metabolic Features of Skeletal Muscle Mitochondria in High-Fat-Diet Fed Rats Producing a Co-adaptation to the Glycolytic Fiber Phenotype

Frontiers in Physiology ◽

10.3389/fphys.2018.00194 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Elena Silvestri ◽

Federica Cioffi ◽

Rita De Matteis ◽

Rosalba Senese ◽

Pieter de Lange ◽

...

Keyword(s):

Skeletal Muscle ◽

High Fat Diet ◽

High Fat ◽

Muscle Mitochondria ◽

Skeletal Muscle Mitochondria

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Functional changes induced by caloric restriction in cardiac and skeletal muscle mitochondria

Journal of Bioenergetics and Biomembranes ◽

10.1007/s10863-020-09838-4 ◽

2020 ◽

Vol 52 (4) ◽

pp. 269-277 ◽

Cited By ~ 2

Author(s):

Julian David C. Serna ◽

Camille C. Caldeira da Silva ◽

Alicia J. Kowaltowski

Keyword(s):

Skeletal Muscle ◽

Caloric Restriction ◽

Muscle Mitochondria ◽

Functional Changes ◽

Skeletal Muscle Mitochondria

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Functional Changes Induced by Short Term Caloric Restriction in Cardiac and Skeletal Muscle Mitochondria

10.1101/2020.03.13.991232 ◽

2020 ◽

Author(s):

Julian David C. Serna ◽

Camille C. Caldeira da Silva ◽

Alicia J. Kowaltowski

Keyword(s):

Skeletal Muscle ◽

Hydrogen Peroxide ◽

Caloric Restriction ◽

Calcium Uptake ◽

Atp Synthesis ◽

Calcium Handling ◽

Muscle Mitochondria ◽

Skeletal Muscle Mitochondria ◽

Uptake Rates ◽

Hydrogen Peroxide Release

AbstractCaloric restriction (CR) is widely known to increase life span and resistance against different types of injuries in several organisms. We have previously shown that mitochondria from livers or brains of CR animals exhibit higher calcium uptake rates and lower sensitivity to calcium-induced mitochondrial permeability transition (mPT), an event related to the resilient phenotype exhibited by these organs. Given the importance of calcium in metabolic control and cell homeostasis, we aimed here to uncover possible changes in mitochondrial calcium handling, redox balance and bioenergetics in cardiac and skeletal muscle mitochondria. Unexpectedly, we found that CR does not alter the susceptibility to mPT in muscle (cardiac or skeletal), nor calcium uptake rates. Despite the lack in changes in calcium transport properties, CR consistently decreased respiration in the presence of ATP synthesis in heart and soleus muscle. In heart, such changes were accompanied by a decrease in respiration in the absence of ATP synthesis, lower maximal respiratory rates and a reduced rate of hydrogen peroxide release. Hydrogen peroxide release was unaltered by CR in skeletal muscle. No changes were observed in inner membrane potentials and respiratory control ratios. Together, these results highlight the tissue-specific bioenergetic and ion transport effects induced by CR, demonstrating that resilience against calcium-induced mPT is not present in all tissues.

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