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Nutrients. 2017 Sep 15;9(9). pii: E1019. 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.

Author information

1
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. wck0007@auburn.edu.
2
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. pwm0009@auburn.edu.
3
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. xzm0012@auburn.edu.
4
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. mzr0049@auburn.edu.
5
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. hwh0001@auburn.edu.
6
Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA. yzz0095@auburn.edu.
7
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. moblecb@auburn.edu.
8
Department of Human Health Performance, University of Montana, Missoula, MT 59812, USA. john.quindry@mso.umt.edu.
9
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. kyoung@auburn.vcom.edu.
10
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. kyoung@auburn.vcom.edu.
11
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. dbeck@auburn.vcom.edu.
12
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. dbeck@auburn.vcom.edu.
13
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. jmartin@auburn.vcom.edu.
14
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. jmartin@auburn.vcom.edu.
15
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. dmccullough@auburn.vcom.edu.
16
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. dmccullough@auburn.vcom.edu.
17
Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, USA. dagostino.dominic1@gmail.com.
18
Applied Sports Performance Institute, Tampa, FL 33607, USA. rlowery@theaspi.com.
19
Applied Sports Performance Institute, Tampa, FL 33607, USA. jwilson@theaspi.com.
20
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. ank0012@auburn.edu.
21
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. ank0012@auburn.edu.
22
School of Kinesiology, Auburn University, Auburn, AL 36849, USA. mdr0024@auburn.edu.
23
Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. mdr0024@auburn.edu.

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.

KEYWORDS:

brain; ketogenic dieting; ketone salts; liver; mitochondria; oxidative stress; skeletal muscle

PMID:
28914762
PMCID:
PMC5622779
DOI:
10.3390/nu9091019
[Indexed for MEDLINE]
Free PMC Article

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