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Nutrients 2017, 9(9), 1019; doi:10.3390/nu9091019

The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats

1
School of Kinesiology, Auburn University, Auburn, AL 36849, USA
2
Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA
3
Department of Human Health Performance, University of Montana, Missoula, MT 59812, USA
4
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine—Auburn Campus, Auburn, AL 36849, USA
5
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, USA
6
Applied Sports Performance Institute, Tampa, FL 33607, USA
*
Authors to whom correspondence should be addressed.
Received: 28 August 2017 / Revised: 11 September 2017 / Accepted: 13 September 2017 / Published: 15 September 2017
(This article belongs to the Special Issue Carbohydrate Metabolism in Health and Disease)
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Abstract

We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the other two groups. In conclusion, short- and long-term KD improves select markers of liver oxidative stress compared to SC feeding, although long-term KD feeding may negatively affect skeletal muscle mitochondrial physiology. View Full-Text
Keywords: ketogenic dieting; ketone salts; skeletal muscle; brain; liver; oxidative stress; mitochondria ketogenic dieting; ketone salts; skeletal muscle; brain; liver; oxidative stress; mitochondria
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MDPI and ACS Style

Kephart, W.C.; Mumford, P.W.; Mao, X.; Romero, M.A.; Hyatt, H.W.; Zhang, Y.; Mobley, C.B.; Quindry, J.C.; Young, K.C.; Beck, D.T.; Martin, J.S.; McCullough, D.J.; D’Agostino, D.P.; Lowery, R.P.; Wilson, J.M.; Kavazis, A.N.; Roberts, M.D. The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats. Nutrients 2017, 9, 1019.

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