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

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.

scholarly journals Sex modulates hepatic mitochondrial adaptations to high-fat diet and physical activity

2019 ◽  
Vol 317 (2) ◽  
pp. E298-E311 ◽  
Author(s):  
Colin S. McCoin ◽  
Alex Von Schulze ◽  
Julie Allen ◽  
Kelly N. Z. Fuller ◽  
Qing Xia ◽  
...  
Keyword(s):  
Physical Activity ◽  
High Fat Diet ◽  
Wheel Running ◽  
Transcriptional Coactivator ◽  
High Fat ◽  
Respiratory Capacity ◽  
Interacting Protein ◽  
Low Fat Diet ◽  
The Impact ◽  
Mitochondrial Adaptations

The impact of sexual dimorphism and mitophagy on hepatic mitochondrial adaptations during the treatment of steatosis with physical activity are largely unknown. Here, we tested if deficiencies in liver-specific peroxisome proliferative activated-receptor-γ coactivator-1α (PGC-1α), a transcriptional coactivator of biogenesis, and BCL-2/ADENOVIRUS EIB 19-kDa interacting protein (BNIP3), a mitophagy regulator, would impact hepatic mitochondrial adaptations (respiratory capacity, H2O2production, mitophagy) to a high-fat diet (HFD) and HFD plus physical activity via voluntary wheel running (VWR) in both sexes. Male and female wild-type (WT), liver-specific PGC-1α heterozygote (LPGC-1α), and BNIP3 null mice were thermoneutral housed (29–31°C) and divided into three groups: sedentary-low-fat diet (LFD), 16 wk of (HFD), or 16 wk of HFD with VWR for the final 8 wk (HFD + VWR) ( n = 5–7/sex/group). HFD did not impair mitochondrial respiratory capacity or coupling in any group; however, HFD + VWR significantly increased maximal respiratory capacity only in WT and PGC-1α females. Males required VWR to elicit mitochondrial adaptations that were inherently present in sedentary females including greater mitochondrial coupling control and reduced H2O2production. Females had overall reduced markers of mitophagy, steatosis, and liver damage. Steatosis and markers of liver injury were present in sedentary male mice on the HFD and were effectively reduced with VWR despite no resolution of steatosis. Overall, reductions in PGC-1α and loss of BNIP3 only modestly impacted mitochondrial adaptations to HFD and HFD + VWR with the biggest effect seen in BNIP3 females. In conclusion, hepatic mitochondrial adaptations to HFD and treatment of HFD-induced steatosis with VWR are more dependent on sex than PGC-1α or BNIP3.

scholarly journals Skeletal muscle mitochondrial and metabolic responses to a high-fat diet in female rats bred for high and low aerobic capacity

2010 ◽  
Vol 35 (2) ◽  
pp. 151-162 ◽  
Author(s):  
Scott P. Naples ◽  
Sarah J. Borengasser ◽  
R. Scott. Rector ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Female Rats ◽  
Mitochondrial Morphology ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Transcriptional Responses ◽  
Peroxisome Proliferator Activated Receptor

Rats selected artificially to be low-capacity runners (LCR) possess a metabolic syndrome phenotype that is worsened by a high-fat diet (HFD), whereas rats selected to be high-capacity runners (HCR) are protected against HFD-induced obesity and insulin resistance. This study examined whether protection against, or susceptibility to, HFD-induced insulin resistance in the HCR–LCR strains is associated with contrasting metabolic adaptations in skeletal muscle. HCR and LCR rats (generation 20; n = 5–6; maximum running distance ∼1800 m vs. ∼350 m, respectively (p < 0.0001)) were divided into HFD (71.6% energy from fat) or normal chow (NC) (16.7% energy from fat) groups for 7 weeks (from 24 to 31 weeks of age). Skeletal muscle (red gastrocnemius) mitochondrial-fatty acid oxidation (FAO), mitochondrial-enzyme activity, mitochondrial-morphology, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and peroxisome proliferator-activated receptor δ (PPARδ) expression and insulin sensitivity (intraperitoneal glucose tolerance tests) were measured. The HFD caused increased adiposity and reduced insulin sensitivity only in the LCR and not the HCR strain. Isolated mitochondria from the HCR skeletal muscle displayed a 2-fold-higher rate of FAO on NC, but both groups increased FAO following HFD. PGC-1α mRNA expression and superoxide dismutase activity were significantly reduced with the HFD in the LCR rats, but not in the HCR rats. PPARδ expression did not differ between strains or dietary conditions. These results do not provide a clear connection between protection of insulin sensitivity and HFD-induced adaptive changes in mitochondrial function or transcriptional responses but do not dismiss the possibility that elevated mitochondrial FAO in the HCR may play a protective role.

Mitochondrial Function and Protein Expression in C5L2KO Mouse Skeletal Muscle after 10 Weeks of High-Fat Diet Intake

2011 ◽  
pp. P3-441-P3-441
Author(s):  
Christian Roy ◽  
Sabina Paglialunga ◽  
Joris Hoeks ◽  
Katherine Cianflone ◽  
Patrick Schrauwen
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
High Fat ◽  
Mouse Skeletal Muscle ◽  
Diet Intake

Insulin sensitivity is independent of lipid binding protein trafficking at the plasma membrane in human skeletal muscle: effect of a 3-day, high-fat diet

2014 ◽  
Vol 307 (9) ◽  
pp. R1136-R1145 ◽  
Author(s):  
Andreas B. Jordy ◽  
Annette K. Serup ◽  
Kristian Karstoft ◽  
Henriette Pilegaard ◽  
Bente Kiens ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Protein Trafficking ◽  
High Fat Diet ◽  
Human Skeletal Muscle ◽  
Lipid Binding ◽  
High Fat ◽  
Before And After ◽  
The Impact ◽  
Sarcolemmal Vesicles

The aim of the present study was to investigate lipid-induced regulation of lipid binding proteins in human skeletal muscle and the impact hereof on insulin sensitivity. Eleven healthy male subjects underwent a 3-day hypercaloric and high-fat diet regime. Muscle biopsies were taken before and after the diet intervention, and giant sarcolemmal vesicles were prepared. The high-fat diet induced decreased insulin sensitivity, but this was not associated with a relocation of FAT/CD36 or FABPpm protein to the sarcolemma. However, FAT/CD36 and FABPpm mRNA, but not the proteins, were upregulated by increased fatty acid availability. This suggests a time dependency in the upregulation of FAT/CD36 and FABPpm protein during high availability of plasma fatty acids. Furthermore, we did not detect FATP1 and FATP4 protein in giant sarcolemmal vesicles obtained from human skeletal muscle. In conclusion, this study shows that a short-term lipid-load increases mRNA content of key lipid handling proteins in human muscle. However, decreased insulin sensitivity after a high-fat diet is not accompanied with relocation of FAT/CD36 or FABPpm protein to the sarcolemma. Finally, FATP1 and FATP4 protein was located intracellularly but not at the sarcolemma in humans.

scholarly journals 12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takahiro Nagatake ◽  
Yuki Shibata ◽  
Sakiko Morimoto ◽  
Eri Node ◽  
Kento Sawane ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Foam Cell ◽  
Linseed Oil ◽  
Cell Formation ◽  
Chronic Inflammatory Disease ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
High Fat ◽  
The Impact

AbstractAtherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

scholarly journals Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high‐fat diet‐induced diabetes

2015 ◽  
Vol 100 (11) ◽  
pp. 1319-1330 ◽  
Author(s):  
Shingo Takada ◽  
Shintaro Kinugawa ◽  
Shouji Matsushima ◽  
Daisuke Takemoto ◽  
Takaaki Furihata ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
High Fat

AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet

2014 ◽  
Vol 117 (8) ◽  
pp. 869-879 ◽  
Author(s):  
Marcia J. Abbott ◽  
Lorraine P. Turcotte
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
High Fat Diet ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Dominant Negative ◽  
Standard Diet ◽  
High Fat ◽  
Palmitate Uptake

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61–64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD.

Epinephrine and AICAR-induced PGC-1α mRNA expression is intact in skeletal muscle from rats fed a high-fat diet

2012 ◽  
Vol 302 (12) ◽  
pp. C1772-C1779 ◽  
Author(s):  
Bruce C. Frier ◽  
Zhongxiao Wan ◽  
Deon B. Williams ◽  
Amanda L. Stefanson ◽  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
High Fat Diet ◽  
Camp Response Element Binding ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Male Wistar Rats ◽  
Amp Activated Protein Kinase

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and is controlled, at least in part, through AMP-activated protein kinase and p38-dependent pathways. There is evidence demonstrating that activation of these kinases and induction of PGC-1α in skeletal muscle are regulated by catecholamines. The purpose of the present study was to determine if consumption of a high-fat diet (HFD) impairs epinephrine and 5-aminoimidazole-4-carboxamide-1β-d-ribofuranoside (AICAR) signaling and induction of PGC-1α in rat skeletal muscle. Male Wistar rats were fed chow or a HFD for 6 wk and then given a weight-adjusted bolus injection of epinephrine (20, 10, or 5 μg/100 g body wt sc) or saline, and triceps muscles were harvested 30 min (signaling) or 2 and 4 h (gene expression) postinjection. Despite blunted increases in p38 phosphorylation, the ability of epinephrine to induce PGC-1α was intact in skeletal muscle from HFD-fed rats and was associated with normal increases in activation of PKA and phosphorylation of cAMP response element-binding protein, reputed mediators of PGC-1α expression. The attenuated epinephrine-mediated increase in p38 phosphorylation was independent of increases in MAPK phosphatase 1. At 2 h following AICAR treatment (0.5 g/kg body wt sc), AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were similar in skeletal muscle from chow- and HFD-fed rats. Surprisingly, AICAR-induced increases in PGC-1α mRNA levels were greater in skeletal muscle from HFD-fed rats. Our results demonstrate that the ability of epinephrine and AICAR to induce PGC-1α remains intact in skeletal muscle from HFD-fed rats. These results question the existence of reduced β-adrenergic responsiveness in diet-induced obesity and demonstrate that increases in p38 phosphorylation are not required for induction of PGC-1α in muscle from obese rats.

scholarly journals Local myostatin inhibition improves skeletal muscle glucose uptake in insulin-resistant high-fat diet-fed mice

2020 ◽  
Vol 319 (1) ◽  
pp. E163-E174
Author(s):  
Wouter Eilers ◽  
David Chambers ◽  
Mark Cleasby ◽  
Keith Foster
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Muscle Hypertrophy ◽  
Glucose Transporter ◽  
Whole Body ◽  
Glucose Disposal ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Myostatin Inhibition

Myostatin inhibition is thought to improve whole body insulin sensitivity and mitigate the development of insulin resistance in models of obesity. However, although myostatin is known to be a major regulator of skeletal muscle mass, the direct effects of myostatin inhibition in muscle on glucose uptake and the mechanisms that may underlie this are still unclear. We investigated the effect of local myostatin inhibition by adeno-associated virus-mediated overexpression of the myostatin propeptide on insulin-stimulated skeletal muscle glucose disposal in chow-fed or high fat diet-fed mice and evaluated the molecular pathways that might mediate this. We found that myostatin inhibition improved glucose disposal in obese high fat diet-fed mice alongside the induction of muscle hypertrophy but did not have an impact in chow-fed mice. This improvement was not associated with greater glucose transporter or peroxisome proliferator-activated receptor-γ coactivator-1α expression or 5′ AMP-activated protein kinase activation as previously suggested. Instead, transcriptomic analysis suggested that the improvement in glucose disposal was associated with significant enrichment in genes involved in fatty acid metabolism and translation of mitochondrial genes. Thus, myostatin inhibition improves muscle insulin-stimulated glucose disposal in obese high fat diet-fed mice independent of muscle hypertrophy, potentially involving previously unidentified pathways.

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