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Article

The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome

1
Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy
2
Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy
3
Animal Facility, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy
4
Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology “S. de Bellis” Research Hospital, 70013 Castellana Grotte, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maurizio Battino
Int. J. Mol. Sci. 2021, 22(7), 3498; https://doi.org/10.3390/ijms22073498
Received: 26 February 2021 / Revised: 23 March 2021 / Accepted: 25 March 2021 / Published: 28 March 2021
Functional alterations in irritable bowel syndrome have been associated with defects in bioenergetics and the mitochondrial network. Effects of high fat, adequate-protein, low carbohydrate ketogenic diet (KD) involve oxidative stress, inflammation, mitochondrial function, and biogenesis. The aim was to evaluate the KD efficacy in reducing the effects of stress on gut mitochondria. Newborn Wistar rats were exposed to maternal deprivation to induce IBS in adulthood. Intestinal inflammation (COX-2 and TRL-4); cellular redox status (SOD 1, SOD 2, PrxIII, mtDNA oxidatively modified purines); mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, mtDNA content); and autophagy (Beclin-1, LC3 II) were evaluated in the colon of exposed rats fed with KD (IBD-KD) or standard diet (IBS-Std), and in unexposed controls (Ctrl). IBS-Std rats showed dysfunctional mitochondrial biogenesis (PPAR-γ, PGC-1α, COX-4, and mtDNA contents lower than in Ctrl) associated with inflammation and increased oxidative stress (higher levels of COX-2 and TLR-4, SOD 1, SOD 2, PrxIII, and oxidatively modified purines than in Ctrl). Loss of autophagy efficacy appeared from reduced levels of Beclin-1 and LC3 II. Feeding of animals with KD elicited compensatory mechanisms able to reduce inflammation, oxidative stress, restore mitochondrial function, and baseline autophagy, possibly via the upregulation of the PPAR-γ/PGC-1α axis. View Full-Text
Keywords: irritable bowel syndrome; ketogenic diet; mitochondria; animal model irritable bowel syndrome; ketogenic diet; mitochondria; animal model
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MDPI and ACS Style

Chimienti, G.; Orlando, A.; Lezza, A.M.S.; D’Attoma, B.; Notarnicola, M.; Gigante, I.; Pesce, V.; Russo, F. The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome. Int. J. Mol. Sci. 2021, 22, 3498. https://doi.org/10.3390/ijms22073498

AMA Style

Chimienti G, Orlando A, Lezza AMS, D’Attoma B, Notarnicola M, Gigante I, Pesce V, Russo F. The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome. International Journal of Molecular Sciences. 2021; 22(7):3498. https://doi.org/10.3390/ijms22073498

Chicago/Turabian Style

Chimienti, Guglielmina, Antonella Orlando, Angela M.S. Lezza, Benedetta D’Attoma, Maria Notarnicola, Isabella Gigante, Vito Pesce, and Francesco Russo. 2021. "The Ketogenic Diet Reduces the Harmful Effects of Stress on Gut Mitochondrial Biogenesis in a Rat Model of Irritable Bowel Syndrome" International Journal of Molecular Sciences 22, no. 7: 3498. https://doi.org/10.3390/ijms22073498

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