Effects of a High Fat Diet and Taurine Supplementation on Metabolic Parameters and Skeletal Muscle Mitochondrial Function in Rats

The current experiment tested the hypothesis that consumption of a high-fat diet (HFD) would differentially affect metabolic parameters in obesity-prone Osborne-Mendel (OM) and obesity-resistant S5B/Pl (S5B) rats. In OM rats consuming a HFD, an increase in HFD intake, body mass, and percent fat mass, and a HFD-induced decrease in metabolic rate and energy expenditure were demonstrated. In S5B rats consuming a HFD, no change in percent body fat or HFD intake was demonstrated and HFD increased metabolic rate and energy expenditure. To assess whether HFD differentially altered skeletal muscle markers of metabolism in OM and S5B rats, the expression of the transporters, CD36 and GLUT4, and the energy sensors, AMPK and PPARγ, in the gastrocnemius muscle was measured. Oxidation and lipid accumulation in the gastrocnemius muscle was histologically determined. Consumption of a HFD decreased phosphorylated AMPK and PPARγ expression in the skeletal muscle of obesity-prone OM rats. Lipid accumulation in skeletal muscle was significantly higher in OM rats fed a HFD. Overall, these data suggest that the differential response to HFD on metabolic rate, energy expenditure, and phosphorylated AMPK and PPARγ in OM and S5B rats, may partially account for differences in the susceptibility to develop obesity.

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Age-related susceptibility to insulin resistance arises from a combination of CPT1B decline and lipid overload

BMC Biology ◽

10.1186/s12915-021-01082-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Marcel A. Vieira-Lara ◽

Marleen B. Dommerholt ◽

Wenxuan Zhang ◽

Maaike Blankestijn ◽

Justina C. Wolters ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Mitochondrial Function ◽

Lipid Accumulation ◽

High Fat Diet ◽

Computational Modelling ◽

High Fat ◽

Aged Mice ◽

Age Related ◽

Intramuscular Lipid

Abstract Background The skeletal muscle plays a central role in glucose homeostasis through the uptake of glucose from the extracellular medium in response to insulin. A number of factors are known to disrupt the normal response to insulin leading to the emergence of insulin resistance (IR). Advanced age and a high-fat diet are factors that increase the susceptibility to IR, with lipid accumulation in the skeletal muscle being a key driver of this phenomenon. It is debated, however, whether lipid accumulation arises due to dietary lipid overload or from a decline of mitochondrial function. To gain insights into the interplay of diet and age in the flexibility of muscle lipid and glucose handling, we combined lipidomics, proteomics, mitochondrial function analysis and computational modelling to investigate young and aged mice on a low- or high-fat diet (HFD). Results As expected, aged mice were more susceptible to IR when given a HFD than young mice. The HFD induced intramuscular lipid accumulation specifically in aged mice, including C18:0-containing ceramides and diacylglycerols. This was reflected by the mitochondrial β-oxidation capacity, which was upregulated by the HFD in young, but not in old mice. Conspicuously, most β-oxidation proteins were upregulated by the HFD in both groups, but carnitine palmitoyltransferase 1B (CPT1B) declined in aged animals. Computational modelling traced the flux control mostly to CPT1B, suggesting a CPT1B-driven loss of flexibility to the HFD with age. Finally, in old animals, glycolytic protein levels were reduced and less flexible to the diet. Conclusion We conclude that intramuscular lipid accumulation and decreased insulin sensitivity are not due to age-related mitochondrial dysfunction or nutritional overload alone, but rather to their combined effects. Moreover, we identify CPT1B as a potential target to counteract age-dependent intramuscular lipid accumulation and thereby IR.

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Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high‐fat diet‐induced obese mice

The FASEB Journal ◽

10.1096/fj.202002394r ◽

2021 ◽

Vol 35 (2) ◽

Author(s):

Jun‐Won Heo ◽

Mi‐Hyun No ◽

Jinkyung Cho ◽

Youngju Choi ◽

Eun‐Jeong Cho ◽

...

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Aerobic Exercise ◽

Mitochondrial Function ◽

High Fat Diet ◽

Aerobic Exercise Training ◽

Obese Mice ◽

High Fat

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Resveratrol attenuates high-fat diet-induced obesity and the aging-related sarcopenia mitochondrial dysfunction in skeletal muscle

10.1101/823088 ◽

2019 ◽

Author(s):

Chyi-Huey Bai ◽

Javad Alizargar ◽

Jia-Ping Wu

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Muscle Mass ◽

Mitochondrial Function ◽

High Fat Diet ◽

Skeletal Muscles ◽

Skeletal Muscle Mass ◽

Sarcopenic Obesity ◽

High Fat ◽

Samp8 Mice

AbstractSarcopenic obesity is a progressive loss of skeletal muscle mass and strength with increases in adiposity. The aim of this study was to investigate the effects of resveratrol on obesity or sarcopenia to potential therapy risk for skeletal muscle declines in physical function. C57BL/6J male mice were fed either a high-fat diet for 4 weeks and resveratrol (low-, middle-, and high-dose) for 8 weeks to express the obesity effect. Samp8 mice sarcopenia skeletal muscle functional deterioration expressed an age-associated decline. Resveratrol (150 mg/Kg BW, daily) was administered by oral gavage two times a week one month of the experimental period. Exercise training based on adaptations in the muscle is training twice a week for 4 weeks. The skeletal muscles from mice in each group were analyzed by H&E staining, TUNEL and western blot analysis to determine mitochondrial function expression, apoptosis and relative fibrosis signaling. Results of the present study indicate that resveratrol in obesity skeletal muscle is linked to an increase in the expression of mitochondrial function involved in Bcl-2 and PI3K/AKT. On the other hand, resveratrol attenuates sarcopenia Samp8 mice, the age-related loss of skeletal muscle mass and mitochondrial function involved in Bad, caspase 3 and IL-6/ERK1. However, exercise training not find a significant difference in sarcopenia skeletal muscles SAMP8 mice. Exercise training didn’t induce sarcopenia skeletal muscle hypertrophy in sarcopenic SAMP8 mice. Therefore, we suggest that resveratrol as a therapeutic potential in the combination of sarcopenia and obesity, the state called sarcopenic obesity.

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Attenuation of obesity and insulin resistance by fish oil supplementation is associated with improved skeletal muscle mitochondrial function in mice fed a high-fat diet

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2017.11.012 ◽

2018 ◽

Vol 55 ◽

pp. 76-88 ◽

Cited By ~ 21

Author(s):

Amanda R. Martins ◽

Amanda R. Crisma ◽

Laureane N. Masi ◽

Catia L. Amaral ◽

Gabriel N. Marzuca-Nassr ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fish Oil ◽

Mitochondrial Function ◽

High Fat Diet ◽

High Fat ◽

Fish Oil Supplementation

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Impact of APOE Genotype on Diet-induced Mitochondrial Adaptations in Mouse Skeletal Muscle

Innovation in Aging ◽

10.1093/geroni/igab046.3491 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 979-979

Author(s):

Niaya James ◽

Oyinkansola Shonde ◽

Nahdia Jones ◽

G William Rebeck ◽

Joanne Allard ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

High Fat Diet ◽

Motor Coordination ◽

Wheel Running ◽

Apoe Genotype ◽

Peroxisome Proliferator ◽

High Fat ◽

Western Blots ◽

The Impact

Abstract Apolipoprotein E (APOE), a component of lipoproteins that facilitates cholesterol transportation, has three variants in the human genome: APOE2, E3, and E4. Prior research found that carriers of APOE4 are more susceptible to developing Alzheimer's disease (AD) and other brain disorders than those who possess other APOE alleles, and that these carriers are also predisposed to mitochondrial impairment– an early characteristic of neuronal dysfunction. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1ɑ) is a major biomarker for mitochondrial biogenesis and function and cytochrome c oxidase subunit IV (COX4) is the terminal enzyme of the mitochondrial respiratory chain. Decreased measures of these proteins indicate reduced mitochondrial function. Aside from genetic inheritance, lifestyle factors such as diet and exercise significantly impact one’s risk for mitochondrial dysfunction and AD. In these studies, we examined the impact of APOE variance on physiological adaptations induced by either exercise or a high-fat diet, with a focus on biomarkers of mitochondrial function. Western blots were used to measure COX4 and PGC-1ɑ levels in skeletal muscle tissue from female APOE3 and APOE4 knock-in transgenic mice. Based on performance on a motorized rotating rod and voluntary wheel-running, we deduced that female APOE4 mice exhibit reduced motor coordination and activity relative to APOE3 mice. APOE4 mice also had reduced COX4 levels that were increased by the high-fat diet. In contrast, COX4 levels in APOE3 mice were reduced in the high-fat diet group. Our data show that diet and APOE genotype interact to produce adaptations in mitochondrial proteins in skeletal muscle.

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