d-allulose provides cardioprotective effect by attenuating cardiac mitochondrial dysfunction in obesity-induced insulin-resistant rats

Abstract Background D-galactose (D-gal) induced ageing has been shown to exacerbate left ventricular (LV) dysfunction via worsening of apoptosis and mitochondrial dysfunction in the heart of obese rats. Hyperbaric oxygen therapy (HBOT) has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in multiple neurological disorders. However, the cardioprotective effect of HBOT on inflammation, apoptosis, LV and mitochondrial functions in D-gal induced ageing rats in the presence of obese-insulin resistant condition has never been investigated. Purpose We sought to determine the effect of HBOT on inflammation, apoptosis, mitochondrial functions and LV function in pre-diabetic rats with D-gal induced ageing. We hypothesized that HBOT attenuates D-gal induced cardiac mitochondrial dysfunctions and reduces inflammation and apoptosis, leading to improved LV function in pre-diabetic rats. Methods Forty-eight male Wistar rats were fed with either normal diet or high-fat diet for 12 weeks. Then, rats were treated with either vehicle groups (0.9% NSS, subcutaneous injection (SC)) or D-gal groups (150 mg/kg/day, SC) for 8 weeks. At week 21, rats in each group were equally divided into 6 sub-groups: normal diet fed rats treated with vehicle (NDV) sham, normal diet fed rats treated with D-gal (NDDg) sham, high fat diet fed rats treated with D-gal (HFDg) sham, high fat diet fed rats treated with vehicle (HFV) + HBOT, NDDg + HBOT and HFDg + HBOT. Sham treated rats were given normal concentration of O2 (flow rate of 80 L/min, 1 ATA for 60 minutes), whereas HBOT treated rats were subjected to 100% O2 (flow rate of 250 L/min, 2 ATA for 60 minutes), given once daily for 2 weeks. Results Under obese-insulin resistant condition, D-gal-induced ageing aggravated LV dysfunction (Fig 1A) and impaired cardiac mitochondrial function, increased cardiac inflammatory and apoptotic markers (Fig 1B). HBOT markedly reduced cardiac TNF-α level and TUNEL positive apoptotic cells, and improved cardiac mitochondrial function as indicated by decreased mitochondrial ROS production, mitochondrial depolarization and mitochondrial swelling, resulting in the restoration of the normal LV function in HFV and NDDg rats, compared to sham NDDg rats. In addition, in HFDg treated rats, HBOT attenuated cardiac TNF-α level, TUNEL positive apoptotic cells and cardiac mitochondrial dysfunction, compared to sham HFDg rats, leading to improved cardiac function as indicated by increased %LV ejection fraction (LVEF) (Figure 1). Conclusion HBOT efficiently alleviates D-gal-induced-age-related LV dysfunction through mitigating inflammation, apoptosis and mitochondrial dysfunction in pre-diabetic rats. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand, 2. Thailand Research Fund Grants

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Chronic treatment with prebiotics, probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats

European Journal of Nutrition ◽

10.1007/s00394-017-1482-3 ◽

2017 ◽

Vol 57 (6) ◽

pp. 2091-2104 ◽

Cited By ~ 30

Author(s):

Wannipa Tunapong ◽

Nattayaporn Apaijai ◽

Sakawdaurn Yasom ◽

Pongpan Tanajak ◽

Keerati Wanchai ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Cardiac Dysfunction ◽

Chronic Treatment ◽

Insulin Resistant

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HIGH-FAT HIGH-CARBOHYDRATE DIET ACCELERATES LEFT-VENTRICULAR DYSFUNCTION FASTER THAN HIGH-FAT DIET ALONE VIA INCREASING MITOCHONDRIAL DYSFUNCTION IN OBESE-INSULIN RESISTANT RATS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(19)31431-7 ◽

2019 ◽

Vol 73 (9) ◽

pp. 824

Author(s):

Nattayaporn Apaijai ◽

Apiwan Arinno ◽

Siripong Palee ◽

Wasana Pratchayasakul ◽

Sasiwan Kerdphoo ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Left Ventricular Dysfunction ◽

High Fat Diet ◽

Ventricular Dysfunction ◽

Left Ventricular ◽

High Carbohydrate Diet ◽

High Fat ◽

Carbohydrate Diet ◽

Insulin Resistant ◽

High Carbohydrate

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Azoramide improves mitochondrial dysfunction in palmitate-induced insulin resistant H9c2 cells

Molecular and Cellular Biochemistry ◽

10.1007/s11010-019-03590-z ◽

2019 ◽

Vol 461 (1-2) ◽

pp. 65-72 ◽

Cited By ~ 1

Author(s):

Esma Nur Okatan ◽

Yusuf Olgar ◽

Erkan Tuncay ◽

Belma Turan

Keyword(s):

Mitochondrial Dysfunction ◽

H9c2 Cells ◽

Insulin Resistant

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Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0255 ◽

2014 ◽

Vol 39 (12) ◽

pp. 1373-1379 ◽

Cited By ~ 18

Author(s):

Hiranya Pintana ◽

Jirapas Sripetchwandee ◽

Luerat Supakul ◽

Nattayaporn Apaijai ◽

Nipon Chattipakorn ◽

...

Keyword(s):

Body Weight ◽

Cognitive Function ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Visceral Fat ◽

Cognitive Deficit ◽

Garlic Extract ◽

Insulin Resistant ◽

Mitochondrial Functions ◽

Brain Mitochondrial Function

Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg–1·day–1) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

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Ticagrelor reverses the mitochondrial dysfunction through preventing accumulated autophagosomes-dependent apoptosis and ER stress in insulin-resistant H9c2 myocytes

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-03731-9 ◽

2020 ◽

Vol 469 (1-2) ◽

pp. 97-107

Author(s):

Yusuf Olgar ◽

Erkan Tuncay ◽

Deniz Billur ◽

Aysegul Durak ◽

Semir Ozdemir ◽

...

Keyword(s):

Er Stress ◽

Mitochondrial Dysfunction ◽

Insulin Resistant

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Sarcopenia from Pathophysiology to Clinical : Literature Review

Biomedical Journal of Indonesia: Jurnal Biomedik Fakultas Kedokteran Universitas Sriwijaya ◽

10.32539/bji.v7i1.261 ◽

2021 ◽

Vol 7 (1) ◽

pp. 125-140

Author(s):

Rachmat Hidayat ◽

Nur Riviati

Keyword(s):

Physical Activity ◽

Literature Review ◽

Mitochondrial Dysfunction ◽

Satellite Cells ◽

Neuromuscular Junctions ◽

Anabolic Resistance ◽

Insulin Resistant ◽

Hormonal Function ◽

Clinical Literature ◽

Reduced Physical Activity

A B S T R A C TThe causes of sarcopenia are thought to be multifactorial including: environmentalfactors, illness, activation of inflammatory pathways, mitochondrial dysfunction, lossof neuromuscular junctions, reduced number of satellite cells and changes in thequality of hormonal function. The mechanism of sarcopenia occurs because the agingprocess coupled with reduced physical activity can cause the formation of cytokinesto increase so that inflammation is easy, insulin resistant, anabolic resistance andneuromuscular impairments.

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Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90287.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. E678-E685 ◽

Cited By ~ 91

Author(s):

Muhammad A. Abdul-Ghani ◽

Florian L. Muller ◽

Yuhong Liu ◽

Alberto O. Chavez ◽

Bogdan Balas ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

Atp Synthesis ◽

Insulin Resistant ◽

Palmitoyl Carnitine ◽

Mitochondrial Inner Membrane ◽

Transport Chain ◽

Mitochondrial Defects ◽

Ffa Metabolism

Insulin resistance is a characteristic feature of type 2 diabetes and obesity. Insulin-resistant individuals manifest multiple disturbances in free fatty acid (FFA) metabolism and have excessive lipid accumulation in insulin target tissues. Although much evidence supports a causal role for altered FFA metabolism in the development of insulin resistance, i.e., “lipotoxicity”, the intracellular mechanisms by which elevated plasma FFA levels cause insulin resistance have yet to be completely elucidated. Recent studies have implicated a possible role for mitochondrial dysfunction in the pathogenesis of insulin resistance in skeletal muscle. We examined the effect of FFA metabolites [palmitoyl carnitine (PC), palmitoyl-coenzyme A (CoA), and oleoyl-CoA] on ATP synthesis in mitochondria isolated from mouse and human skeletal muscle. At concentrations ranging from 0.5 to 2 μM, these FFA metabolites stimulated ATP synthesis; however, above 5 μM, there was a dose-response inhibition of ATP synthesis. Furthermore, 10 μM PC inhibits ATP synthesis from pyruvate. Elevated PC concentrations (≥10 μM) inhibit electron transport chain activity and decrease the mitochondrial inner membrane potential. These acquired mitochondrial defects, caused by a physiological increase in the concentration of FFA metabolites, provide a mechanistic link between lipotoxicity, mitochondrial dysfunction, and muscle insulin resistance.

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Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats

Journal of Endocrinology ◽

10.1530/joe-16-0406 ◽

2017 ◽

Vol 232 (2) ◽

pp. 189-204 ◽

Cited By ~ 10

Author(s):

Pongpan Tanajak ◽

Hiranya Pintana ◽

Natthaphat Siri-Angkul ◽

Juthamas Khamseekaew ◽

Nattayaporn Apaijai ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Rate ◽

Heart Rate Variability ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Cardiac Dysfunction ◽

Metabolic Regulation ◽

Left Ventricular ◽

Lv Function ◽

Insulin Resistant

Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling pathway were determined. Rats on a HFD developed insulin and FGF21 resistance, oxidative stress, cardiac mitochondrial dysfunction and impaired LV function. Rats on CR alone showed both decreased body weight and visceral fat accumulation, whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative stress. However, vildagliptin improved heart rate variability (HRV), cardiac mitochondrial function and LV function better than the CR. Chronic HFD consumption leads to obese-insulin resistance and FGF21 resistance. Although CR is effective in improving metabolic regulation, vildagliptin provides greater efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21 signaling pathways and attenuating cardiac mitochondrial dysfunction in obese-insulin-resistant rats.

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