Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction

SUMMARYAging is associated with central fat redistribution, and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stemcells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y).Aged-donor ASCs showed more intense features of aging (senescence, mitochondrial dysfunction, and oxidative stress) than young-donor ASCs. Oxidative stress and mitochondrial dysfunction occurred earlier in adipocytes derived from aged-donor than from young-donor ASCs, leading to insulin resistance and impaired adipogenesis.When aged-donor ASCs were treated with metformin, senescence, oxidative stress and mitochondrial dysfunction returned to the levels observed in young-donor ASCs. Furthermore, metformin’s prevention of senescence and dysfunction during ASC proliferation restored the cells’ adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase.We show here that targeting senescent ASCs from aged women with metformin may alleviate age-related dysfunction, insulin resistance, and impaired adipogenesis.

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Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

Journal of Clinical Medicine ◽

10.3390/jcm8091385 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1385 ◽

Cited By ~ 48

Author(s):

Burgos-Morón ◽

Abad-Jiménez ◽

Marañón ◽

Iannantuoni ◽

Escribano-López ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Er Stress ◽

Mitochondrial Dysfunction ◽

Current Knowledge ◽

Β Cells ◽

The Relationship ◽

And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

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Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1948602 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Anastasia Agapouda ◽

Veronika Butterweck ◽

Matthias Hamburger ◽

Dalene de Beer ◽

Elizabeth Joubert ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Hot Water ◽

Human Neuroblastoma ◽

Atp Production ◽

Physiological Conditions ◽

Age Related ◽

Mitochondrial Functions ◽

Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

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Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽

10.3390/antiox8040109 ◽

2019 ◽

Vol 8 (4) ◽

pp. 109 ◽

Cited By ~ 14

Author(s):

Chisato Fujimoto ◽

Tatsuya Yamasoba

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Mitochondrial Dysfunction ◽

Cell Lines ◽

Mitochondrial Gene ◽

Protective Effects ◽

Drug Induced ◽

Age Related ◽

Cochlear Damage ◽

Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

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Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease

Mediators of Inflammation ◽

10.1155/2015/105828 ◽

2015 ◽

Vol 2015 ◽

pp. 1-17 ◽

Cited By ~ 184

Author(s):

Giuseppe Verdile ◽

Kevin N. Keane ◽

Vinicius F. Cruzat ◽

Sandra Medic ◽

Miheer Sabale ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Insulin Resistance ◽

Alzheimer's Disease ◽

Insulin Signalling ◽

Contributory Factor ◽

Protein Accumulation ◽

Age Related ◽

Impaired Insulin ◽

And Oxidative Stress

Type 2 diabetes (T2DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β(Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.

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Tartary buckwheat flavonoids ameliorate high fructose-induced insulin resistance and oxidative stress associated with the insulin signaling and Nrf2/HO-1 pathways in mice

Food & Function ◽

10.1039/c7fo00359e ◽

2017 ◽

Vol 8 (8) ◽

pp. 2803-2816 ◽

Cited By ~ 15

Author(s):

Yuanyuan Hu ◽

Zuoxu Hou ◽

Ruokun Yi ◽

Zhongming Wang ◽

Peng Sun ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Drinking Water ◽

Insulin Signaling ◽

Tartary Buckwheat ◽

Hepatic Oxidative Stress ◽

High Fructose ◽

Flavonoid Fraction ◽

And Oxidative Stress

The present study was conducted to explore the effects of a purified tartary buckwheat flavonoid fraction (TBF) on insulin resistance and hepatic oxidative stress in mice fed high fructose in drinking water (20%) for 8 weeks.

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JNK Activation of BIM Promotes Hepatic Oxidative Stress, Steatosis, and Insulin Resistance in Obesity

Diabetes ◽

10.2337/db17-0348 ◽

2017 ◽

Vol 66 (12) ◽

pp. 2973-2986 ◽

Cited By ~ 9

Author(s):

Sara A. Litwak ◽

Lokman Pang ◽

Sandra Galic ◽

Mariana Igoillo-Esteve ◽

William J. Stanley ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Hepatic Oxidative Stress ◽

Jnk Activation

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The effect of resveratrol on insulin resistance, metabolic syndrome and hepatic oxidative stress in fructose- fed rats

Bulletin of Egyptian Society for Physiological Sciences ◽

10.21608/besps.2014.34020 ◽

2014 ◽

Vol 34 (1) ◽

pp. 27-42

Author(s):

Ahmed Abdalfattah

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Hepatic Oxidative Stress

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Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

Journal of Endocrinology ◽

10.1530/joe-18-0552 ◽

2019 ◽

Vol 241 (1) ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Jirapas Sripetchwandee ◽

Hiranya Pintana ◽

Piangkwan Sa-nguanmoo ◽

Chiraphat Boonnag ◽

Wasana Pratchayasakul ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Cognitive Decline ◽

Mitochondrial Dysfunction ◽

Dendritic Spine ◽

High Fat Diet ◽

High Fat ◽

Long Term Depression ◽

Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

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