دورية أكاديمية
Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?
| العنوان: | Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe? |
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| المؤلفون: | Nunn, AVW, Bell, JD, Guy, GW |
| المصدر: | 26 ; 1 |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2009 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Nutrition & Dietetics, ACTIVATED PROTEIN-KINASE, NF-KAPPA-B, TRANSCRIPTION FACTOR FOXO1, ENDOPLASMIC-RETICULUM STRESS, PROMOTES MITOCHONDRIAL BIOGENESIS, POLYUNSATURATED FATTY-ACIDS, HIGH-DENSITY-LIPOPROTEIN, VISCERAL ADIPOSE-TISSUE, NITRIC-OXIDE SYNTHASE, ACUTE-PHASE REACTANTS, 0606 Physiology, 1106 Human Movement and Sports Sciences, 1111 Nutrition and Dietetics |
| الوصف: | The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress) signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility) may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest that as oxidative stress determines functional longevity, a rather more ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1743-7075 |
| العلاقة: | Nutrition and Metabolism; http://hdl.handle.net/10044/1/80084Test |
| DOI: | 10.1186/1743-7075-6-16 |
| الإتاحة: | https://doi.org/10.1186/1743-7075-6-16Test http://hdl.handle.net/10044/1/80084Test |
| حقوق: | © 2009 Nunn et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0Test), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| رقم الانضمام: | edsbas.E65443A6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17437075 |
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| DOI: | 10.1186/1743-7075-6-16 |