1. Common and divergent molecular mechanisms of fasting and ketogenic diets.
- Author
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Paoli, Antonio, Tinsley, Grant M., Mattson, Mark P., De Vivo, Immaculata, Dhawan, Ravi, and Moro, Tatiana
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KETOGENIC diet , *PROTEIN kinases , *LEPTIN , *INTERMITTENT fasting , *KETONES , *AMP-activated protein kinases , *PYRIN (Protein) , *ACETONEMIA - Abstract
Fasting can be divided into intermittent short-term fasting (ISTF; frequent fasts lasting <24 h) and long-term fasting (LTF; fasts lasting >24 h and up to several weeks). ISTF extends lifespan and ameliorates a wide range of diseases in animal models. ISTF and ketogenic diets (KDs) reduce oxidative stress by direct actions on the mitochondria and by inducing the expression of antioxidant enzymes. The ketone body β-hydroxybutyrate suppresses inflammation by inhibiting the nucleotide oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome. Human clinical trials demonstrated disease-modifying effects of ISTF in obesity, diabetes, and chronic inflammatory disorders. Frequent switching between ketogenic and nonketogenic states may optimize health and resilience. Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases (HDACs), reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality. Intermittent short-term fasting (ISTF) and ketogenic diets (KDs) exert overlapping but not identical effects on cell metabolism, function, and resilience. Whereas health benefits of KD are largely mediated by the ketone bodies (KBs), ISTF engages additional adaptive physiological responses. KDs act mainly through inhibition of histone deacetylases, reduction of oxidative stress, improvement of mitochondria efficiency, and control of inflammation. Mechanisms of action of ISTF include stimulation of autophagy, increased insulin and leptin sensitivity, activation of AMP-activated protein kinase (AMPK), inhibition of the mechanistic target of rapamycin (mTOR) pathway, bolstering mitochondrial resilience, and suppression of oxidative stress and inflammation. Frequent switching between ketogenic and nonketogenic states may optimize health by increasing stress resistance, while also enhancing cell plasticity and functionality. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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