scholarly journals Diabetic Pregnancy and Maternal High-Fat Diet Impair Mitochondrial Dynamism in the Developing Fetal Rat Heart by Sex-Specific Mechanisms

2019 ◽  
Vol 20 (12) ◽  
pp. 3090 ◽  
Author(s):  
Tricia D. Larsen ◽  
Kyle H. Sabey ◽  
Alexis J. Knutson ◽  
Tyler C. T. Gandy ◽  
Eli J. Louwagie ◽  
...  
Keyword(s):  
Prenatal Exposure ◽  
High Fat Diet ◽  
Mitochondrial Dynamics ◽  
Systolic Dysfunction ◽  
Maternal Diabetes ◽  
Neonatal Rat ◽  
Prenatally Exposed ◽  
High Fat ◽  
Rat Cardiomyocytes ◽  
Gender Specific

Infants born to diabetic or obese mothers are at greater risk of heart disease at birth and throughout life, but prevention is hindered because underlying mechanisms remain poorly understood. Using a rat model, we showed that prenatal exposure to maternal diabetes and a high-fat diet caused diastolic and systolic dysfunction, myocardial lipid accumulation, decreased respiratory capacity, and oxidative stress in newborn offspring hearts. This study aimed to determine whether mitochondrial dynamism played a role. Using confocal live-cell imaging, we examined mitochondrial dynamics in neonatal rat cardiomyocytes (NRCM) from four prenatally exposed groups: controls, diabetes, high-fat diet, and combination exposed. Cardiac expression of dynamism-related genes and proteins were compared, and gender-specific differences were evaluated. Findings show that normal NRCM have highly dynamic mitochondria with a well-balanced number of fusion and fission events. Prenatal exposure to diabetes or a high-fat diet impaired dynamism resulting in shorter, wider mitochondria. Mechanisms of impaired dynamism were gender-specific and protein regulated. Females had higher expression of fusion proteins which may confer a cardioprotective effect. Prenatally exposed male hearts had post-translational modifications known to impair dynamism and influence mitophagy-mediated cell death. This study identifies mitochondrial fusion and fission proteins as targetable, pathogenic regulators of heart health in offspring exposed to excess circulating maternal fuels.

Repercussion of Maternal Diabetes and Post-Weaning High-Fat Diet Consumption in Laboratory Animals

Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154652
Author(s):  
Veronyca G. Paula ◽  
Yuri K. Sinzato ◽  
Rafaianne Q.M. Souza ◽  
Larissa L. Cruz ◽  
Eduardo Kloppel ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Maternal Diabetes ◽  
Laboratory Animals ◽  
High Fat

scholarly journals Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction

2014 ◽  
Vol 112 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Ruifang Sun ◽  
Xiaoming Wang ◽  
Yan Liu ◽  
Min Xia
Keyword(s):  
Endothelial Cell ◽  
Fish Oil ◽  
High Fat Diet ◽  
Mitochondrial Dynamics ◽  
Atherosclerotic Lesion ◽  
Partial Replacement ◽  
Lesion Volume ◽  
High Fat ◽  
Endothelial Cell Function ◽  
Expression Levels

Diets supplemented with fish oil (FO), which is rich in n-3 PUFA, have been shown to modify several key risk factors for CVD. The purpose of the present study was to determine the effect of FO supplementation on mitochondrial dynamic protein expression in the endothelium and on endothelial cell function. Male apoE-deficient (apoE− / −) mice (8 weeks old, n 12 per group) were fed a high-fat diet containing 45 % fat (HFD group) or a HFD with partial replacement of lard with 10 % (w/w) FO (FO group) (total EPA and DHA content 64·1 g/kg) for 8 weeks. ApoE− / − mice in the FO group had a greater endothelium-dependent vasorelaxation response to acetylcholine (Ach) than those in the HFD group. The atherosclerotic lesion volume in the aortic sinus of mice in the FO group was 54 % lower than that in the HFD group (P< 0·01). In addition, the aortas isolated from mice in the FO group had higher expression levels of Mfn2 and Opa1 but lower expression levels of Fis1 than those from the HFD group. Compared with mice fed the HFD, those fed the FO diet showed significantly lower levels of mitochondrial oxidative stress, cytochrome c release and caspase-3 activity (each P< 0·05). Furthermore, FO-fed mice displayed increased NO release and availability and enhanced endothelial NO synthase activity compared with HFD-fed mice. Taken together, these results reveal a novel mechanism by which FO protects against endothelial cell dysfunction, which may result in improved mitochondrial dynamics.

scholarly journals In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

2014 ◽  
Vol 46 (23) ◽  
pp. 841-850 ◽  
Author(s):  
Sarah J. Borengasser ◽  
Jennifer Faske ◽  
Ping Kang ◽  
Michael L. Blackburn ◽  
Thomas M. Badger ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Maternal Obesity ◽  
Mitochondrial Dynamics ◽  
Later Life ◽  
In Utero ◽  
Mitochondrial Morphology ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Offspring

The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (∼16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)α, PGC1β, and estrogen-related receptor (ERR)α], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.

scholarly journals Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Atsushi Morio ◽  
Rie Tsutsumi ◽  
Shiho Satomi ◽  
Takashi Kondo ◽  
Hirotsugu Miyoshi ◽  
...  
Keyword(s):  
Infarct Size ◽  
High Fat Diet ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fusion ◽  
Control Group ◽  
Obese Mice ◽  
High Fat ◽  
Rat Cardiomyocytes ◽  
Cardioprotective Effects ◽  
Mtor Activity

Abstract Background Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.

scholarly journals Low-Intensity Exercise Training Additionally Increases Mitochondrial Dynamics Caused by High-Fat Diet (HFD) but Has No Additional Effect on Mitochondrial Biogenesis in Fast-Twitch Muscle by HFD

2020 ◽  
Vol 17 (15) ◽  
pp. 5461
Author(s):  
Yun Seok Kang ◽  
Donghun Seong ◽  
Jae Cheol Kim ◽  
Sang Hyun Kim
Keyword(s):  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
High Fat Diet ◽  
Mitochondrial Dynamics ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Related Factors ◽  
Mitochondrial Dynamic ◽  
Low Intensity

This study examines how the high-fat diet (HFD) affects mitochondrial dynamics and biogenesis, and also whether combining it with low-intensity endurance exercise adds to these effects. Six 8-week-old male Sprague–Dawley (SD) rats were put on control (CON; standard chow diet), HF (HFD intake), and HFEx (HFD + low-intensity treadmill exercise) for 6 weeks. As a result, no change in body weight was observed among the groups. However, epididymal fat mass increased significantly in the two groups that had been given HFD. Blood free fatty acid (FFA) also increased significantly in the HF group. While HFD increased insulin resistance (IR), this was improved significantly in the HFEx group. HFD also significantly increased mitochondrial biogenesis-related factors (PPARδ, PGC-1α, and mtTFA) and mitochondrial electron transport chain proteins; however, no additional effect from exercise was observed. Mitochondrial dynamic-related factors were also affected: Mfn2 increased significantly in the HFEx group, while Drp1 and Fis-1 increased significantly in both the HF and HFEx groups. The number of mitochondria in the subsarcolemmal region, and their size in the subsarcolemmal and intermyofibrillar regions, also increased significantly in the HFEx group. Taken overall, these results show that HFD in combination with low-intensity endurance exercise has no additive effect on mitochondrial biogenesis, although it does have such an effect on mitochondrial dynamics by improving IR.

Exposure to maternal hyperglycemia and high-fat diet consumption after weaning in rats: repercussions on periovarian adipose tissue

2021 ◽  
pp. 1-8
Author(s):  
Carolina M. Saullo ◽  
Yuri K. Sinzato ◽  
Verônyca G. Paula ◽  
Franciane Q. Gallego ◽  
José E. Corrente ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Adult Life ◽  
Maternal Diabetes ◽  
Female Offspring ◽  
Standard Diet ◽  
High Fat ◽  
Intrauterine Environment ◽  
Tissue Samples ◽  
Maternal Hyperglycemia

Abstract Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.

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