Palmitate but Not Oleate Exerts a Negative Effect on Oxygen Utilization in Myoblasts of Patients with the m.3243A>G Mutation: A Pilot Study

It is known that exposure to excess saturated fatty acids, especially palmitate, can trigger cellular stress responses interpreted as lipotoxicity. The effect of excessive free fatty acids on oxidative phosphorylation capacity in myoblasts of patients with the m.3243A>G mutation was evaluated with the mitochondrial (Mito) stress test using a Seahorse XF96 analyzer. ß-oxidation, measured with the Seahorse XF96 analyzer, was similar in patients and controls, and reduced in both patients and controls at 40 °C compared to 37 °C. Mito stress test in the absence of fatty acids showed lower values in patients compared to controls. The mitochondrial activity and ATP production rates were significantly reduced in presence of palmitate, but not of oleate in patients, showing a negative effect of excessive palmitate on mitochondrial function in patients. Diabetes mellitus is a frequent symptom in patients with m.3243A>G mutation. It can be speculated that the negative effect of palmitate on mitochondrial function might be related to diacylglycerols (DAG) and ceramides (CER) mediated insulin resistance. This might contribute to the elevated risk for diabetes mellitus in m.3243A>G patients.

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Bioenergetic and metabolic impairments in Duchenne Muscular Dystrophy (DMD) patients' iPSC-derived cardiomyocytes

European Heart Journal ◽

10.1093/ehjci/ehaa946.3709 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

L Willi ◽

B Agranovich ◽

I Abramovich ◽

D Freimark ◽

M Arad ◽

...

Keyword(s):

Stress Test ◽

Young Male ◽

Induced Pluripotent Stem Cell ◽

Dystrophin Gene ◽

Energy System ◽

Basal Respiration ◽

Mitochondrial Activity ◽

Funding Source ◽

Atp Production ◽

Metabolic Impairments

Abstract Introduction DMD, an X-linked muscle degenerative fatal disease, is caused by mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in DMD patients. Treatments for DCM in DMD are limited to steroids and standard heart failure medications such as β-blockers and ACE-inhibitors, and therefore novel therapeutic modalities are urgently needed. Purpose We hypothesized that dystrophin mutations in DMD lead to cardiomyopathy-causing bioenergetic/metabolic impairments, which can be therapeutically targeted for improving cardiac function. Methods Induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) were generated from healthy volunteer and 3 DMD patients: young male (YM), adult male (AM) and adult female (AF). We investigated the bioenergetics, electrophysiology, mitochondrial and metabolic features of healthy and DMD iPSC-CMs using the Seahorse Flux analyzer, patch clamp, confocal fluorescence microscopy and Liquid chromatography mass spectrometry (LC-MS) technologies, respectively. Results To test the hypothesis, we measured respiration and glycolytic rates of healthy and DMD iPSC-CMs. Compared to healthy iPSC-CMs, in both AM and AF DMD, but not in YM DMD cardiomyocytes, there was a 75% decrease in ATP production, and 80% and 45% decrease in basal respiration, respectively. In agreement with the healthy-like bioenergetic status of YM, the iPSC-CMs showed no arrhythmias, in contrast to the prominent arrhythmias in AM and AF cardiomyocytes. To determine whether the impairment in the phosphorylation pathway (OXPHOS) affects glycolysis, we measured the cardiomyocytes' response to glycolytic stress test. These experiments showed that the glycolytic rates were similar in healthy and DMD iPSC-CMs. In agreement with impaired OXPHOS, mitochondrial activity measured by 3D life confocal microscopy was attenuated in the DMD male by 35%, compared to healthy cardiomyocytes. Furthermore, the metabolomic LC-MS analyses demonstrated significant differences in metabolite levels in YM, AM and AF DMD iPSC-CMs relative to healthy iPSC-CMs. For example, compared to healthy iPSC-CMs, there was a dramatic fall to undetected levels in phosphocreatine in both AM and AF, but not in YM DMD, indicating a dysfunctional phosphocreatine energy system. Conclusions DMD iPSC-CMs exhibit bioenergetic/metabolic impairments, which constitute novel targets for alleviating the cardiomyopathy in DMD patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ISF - Israel Science Foundation

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The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22168680 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8680

Author(s):

Kamila Misiakiewicz-Has ◽

Dominika Maciejewska-Markiewicz ◽

Sylwia Rzeszotek ◽

Anna Pilutin ◽

Agnieszka Kolasa ◽

...

Keyword(s):

Diabetes Mellitus ◽

Fatty Acids ◽

Lipid Profile ◽

Plasma Glucose ◽

Plasma Lipid ◽

Tribulus Terrestris ◽

Plasma Lipid Profile ◽

Negative Effect ◽

Liver Morphology

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague–Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.

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Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

Biochemical Journal ◽

10.1042/bj20130863 ◽

2014 ◽

Vol 457 (3) ◽

pp. 415-424 ◽

Cited By ~ 116

Author(s):

Marthe H. R. Ludtmann ◽

Plamena R. Angelova ◽

Ying Zhang ◽

Andrey Y. Abramov ◽

Albena T. Dinkova-Kostova

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Saturated Fatty Acids ◽

Acid Oxidation ◽

Mitochondrial Fatty Acid Oxidation ◽

Atp Production ◽

Mitochondrial Fatty Acid ◽

Mitochondrial Oxidation ◽

Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

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The parallel comparative study of metabolism of fatty acids in erythrocytes and other tissues under experimental diabetes mellitus

Medical Journal of the Russian Federation ◽

10.18821/0869-2106-2017-23-1-27-30 ◽

2017 ◽

Vol 23 (1) ◽

pp. 27-30

Author(s):

Nina P. Mikaelyan ◽

Z. Kh Nguen ◽

O. S Komarov ◽

K. A Mikaelyan

Keyword(s):

Diabetes Mellitus ◽

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Experimental Diabetes ◽

Saturated Fatty Acids ◽

Early Period ◽

Streptozotocin Diabetes ◽

Peroxidation Of Lipids ◽

Muscular Tissue ◽

Experimental Diabetes Mellitus

The parallel study of impact of Streptozotocin diabetes mellitus on level of lipids and content of fatty acids in blood, in homogenates of skin, liver and muscular tissue in conditions of oxidative stress demonstrated that in rats at early period of development of diabetes mellitus alongside with hypertriglyceridimia and hypercholesterolimia, significant alterations are observed in content of fatty acids of blood and homogenates of analyzed tissues. The alterations are accompanied with peroxidation of lipids and decreasing of activity of enzymes-antioxidants and also decreasing of degree of utilization of glucose by erythrocytes. under experimental diabetes mellitus significant increasing of saturated fatty acids, especially palmitic fatty acid, results in decreasing of level of mono unsaturated fatty acids (at the expense of oleic fatty acids) that significantly differs of corresponding spectrum in patients with diabetes mellitus. The results of study also testify that already at early stages of development of diabetes mellitus alterations in pool of fatty acids of erythrocytes and homogenates of liver, skin and cardiac muscle similar (with slightly differences) and in all analyzed tissues disorders of fatty acids metabolism are characterized by atherosclerotic direction.

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Determination of fatty acid composition content in the herbal antidiabetic collections

Pharmacia ◽

10.3897/pharmacia.67.e51812 ◽

2020 ◽

Vol 67 (3) ◽

pp. 153-159

Author(s):

Alona Savych ◽

Svetlana Marchyshyn ◽

Roksolana Basaraba

Keyword(s):

Diabetes Mellitus ◽

Fatty Acids ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Diabetes Mellitus Type 2 ◽

Saturated Fatty Acids ◽

Diabetes Mellitus Type ◽

Raw Material

It was determined the qualitative composition and the quantitative content of fatty acids in the herbal antidiabetic collection № 3, № 4, № 7, № 13, № 19, which are used in folk medicine for prevention and treatment of diabetes mellitus type 2 in Ukraine by GC/MS method. According to the results it was identified 8 fatty acids in the herbal antidiabetic collection № 3, 13 fatty acids in the herbal antidiabetic collection № 4, 12 fatty acids in the herbal antidiabetic collection № 7, 13 fatty acids in the herbal antidiabetic collection № 13 and 11 fatty acids in the herbal antidiabetic collection № 19. The saturated fatty acids were found to be dominated in the raw plant material. The results of the quantitative research showed that the herbal antidiabetic collection № 3 contains 16.13 mg/g of fatty acids, the herbal antidiabetic collection № 4 – 27.17 mg/g, the herbal antidiabetic collection № 7 – 31.98 mg/g, the herbal antidiabetic collection № 13 – 27.37 mg/g, the herbal antidiabetic collection № 19 – 18.79 mg/g. The GC/MS analysis of the fatty acid composition in the herbal antidiabetic collections has shown that this raw material has a lot of fatty acids, which can have a positive effect for the treatment and prevention of diabetes mellitus type 2.

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Calorie Restriction Maintains Mitochondrial Function and Redox Balance Avoiding Lipidomic Reprogramming during Isoproterenol-Induced Cardiac Hypertrophy

10.1101/2021.07.13.452233 ◽

2021 ◽

Author(s):

Cícera Edna Barbosa David ◽

Aline Maria Brito Lucas ◽

Pedro Lourenzo Oliveira Cunha ◽

Yuana Ivia Ponte Viana ◽

Marcos Yukio Yoshinaga ◽

...

Keyword(s):

Fatty Acids ◽

Cardiac Hypertrophy ◽

Calorie Restriction ◽

Mitochondrial Function ◽

Cardiac Tissue ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Respiratory Control ◽

H2o2 Production

Cardiac hypertrophy induces a metabolic shift, leading to a preferential consumption of glucose (over fatty acids) to support the high energetic demand. Typically, health cardiac tissue utilizes more fat than any other organ. Calorie restriction is a dietary procedure that induces health benefits and lifespan extension in many organisms. Given the beneficial effects of calorie restriction and the metabolic dysregulation seen during cardiac hypertrophy, we hypothesized that calorie restriction prevents cardiac hypertrophy, lipid, mitochondrial, and redox dysregulations. Strikingly, calorie restriction reversed isoproterenol-induced cardiac hypertrophy, lowered succinate driven mitochondrial H2O2 production, improved mitochondrial function (indicated as a higher Respiratory Control Ratio – RCR) and avoided mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) repression. To gain insight into how calorie restriction could interfere with the metabolic changes induced by cardiac hypertrophy, we performed lipidomic profiling. Calorie restriction protected against the consumption of several triglycerides (TG) linked to unsaturated fatty acids, and the accumulation of TGs containing saturated fatty acids observed in hypertrophic samples. Cardiac hypertrophy induced an increase in ceramides, phosphoethanolamines and acylcarnitines (12:0, 14:0, 16:0 and 18:0) that were also reversed by calorie restriction. Altogether, our data demonstrate that hypertrophy changes the cardiac lipidome, causes mitochondrial disturbances and oxidative stress. All these changes are prevented by calorie restriction intervention in vivo. This study uncovers calorie restriction as a resource protect cardiac tissue and prevent cardiac hypertrophy-induced lipidomic remodeling.

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Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.624216 ◽

2021 ◽

Vol 8 ◽

Author(s):

Daniela Ramaccini ◽

Vanessa Montoya-Uribe ◽

Femke J. Aan ◽

Lorenzo Modesti ◽

Yaiza Potes ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Mitochondrial Function ◽

Reading Ability ◽

Cardiac Tissue ◽

Mitochondrial Activity ◽

Atp Production ◽

Energy Demands ◽

Proof Reading ◽

Mitochondrial Functions ◽

Optimal Function

Cardiac tissue requires a persistent production of energy in order to exert its pumping function. Therefore, the maintenance of this function relies on mitochondria that represent the “powerhouse” of all cardiac activities. Mitochondria being one of the key players for the proper functioning of the mammalian heart suggests continual regulation and organization. Mitochondria adapt to cellular energy demands via fusion-fission events and, as a proof-reading ability, undergo mitophagy in cases of abnormalities. Ca2+ fluxes play a pivotal role in regulating all mitochondrial functions, including ATP production, metabolism, oxidative stress balance and apoptosis. Communication between mitochondria and others organelles, especially the sarcoplasmic reticulum is required for optimal function. Consequently, abnormal mitochondrial activity results in decreased energy production leading to pathological conditions. In this review, we will describe how mitochondrial function or dysfunction impacts cardiac activities and the development of dilated cardiomyopathy.

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Saturated fatty acids accelerate linear motility through mitochondrial ATP production in bull sperm

Reproductive Medicine and Biology ◽

10.1002/rmb2.12381 ◽

2021 ◽

Author(s):

Md. Mazharul Islam ◽

Takashi Umehara ◽

Natsumi Tsujita ◽

Masayuki Shimada

Keyword(s):

Fatty Acids ◽

Saturated Fatty Acids ◽

Atp Production ◽

Bull Sperm

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The Influence of Nutrition on Adiponectin—A Narrative Review

Nutrients ◽

10.3390/nu13051394 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1394

Author(s):

Justyna Janiszewska ◽

Joanna Ostrowska ◽

Dorota Szostak-Węgierek

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Dietary Habits ◽

Saturated Fatty Acids ◽

Monounsaturated Fatty Acids ◽

Dietary Factors ◽

Omega 3 ◽

Endocrine Organ ◽

Low Fat Diet ◽

Negative Effect

The adipose tissue is an active endocrine organ which synthesizes and secretes a variety of adipokines, including adiponectin with its anti-inflammatory properties. Its expression is influenced by numerous factors such as age, sex, body weight and adipose tissue content. However, dietary factors, i.e., diet structure and the percentage of individual nutrients and products, are very important modulators. Beneficial dietary habits are the Mediterranean diet, DASH diet, diet based on plant products and diet with reduced energy value. Moreover, the share of individual products and nutrients which increase the concentration of adiponectin is worth noting. This group may include monounsaturated fatty acids, polyunsaturated omega-3 fatty acids, dietary fiber, polyphenols, alcohol and milk products. Conversely, dietary ingredients which have a negative effect on the concentration of adiponectin are typical components of the Western diet: saturated fatty acids, trans fatty acids, monosaccharides and disaccharides, and red meat. Furthermore, a diet characterized by a high glycemic index such as a high-carbohydrate low-fat diet also seems to be unfavorable. Due to the fact that available knowledge should be systematized, this study aimed to summarize the most recent research on the influence of dietary factors on the concentration of adiponectin.

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