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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(9)N

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.

Authors+Show Affiliations

School of Kinesiology, Auburn University, Auburn, AL 36849, USA. wck0007@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. pwm0009@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. xzm0012@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. mzr0049@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. hwh0001@auburn.edu.Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA. yzz0095@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. moblecb@auburn.edu.Department of Human Health Performance, University of Montana, Missoula, MT 59812, USA. john.quindry@mso.umt.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. kyoung@auburn.vcom.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. kyoung@auburn.vcom.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. dbeck@auburn.vcom.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. dbeck@auburn.vcom.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. jmartin@auburn.vcom.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. jmartin@auburn.vcom.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. dmccullough@auburn.vcom.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. dmccullough@auburn.vcom.edu.Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, USA. dagostino.dominic1@gmail.com.Applied Sports Performance Institute, Tampa, FL 33607, USA. rlowery@theaspi.com.Applied Sports Performance Institute, Tampa, FL 33607, USA. jwilson@theaspi.com.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. ank0012@auburn.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. ank0012@auburn.edu.School of Kinesiology, Auburn University, Auburn, AL 36849, USA. mdr0024@auburn.edu. Department of Cell Biology and Physiology, Edward via College of Osteopathic Medicine-Auburn Campus, Auburn, AL 36849, USA. mdr0024@auburn.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28914762

Citation

Kephart, Wesley C., et al. "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, vol. 9, no. 9, 2017.
Kephart WC, Mumford PW, Mao X, et al. 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(9).
Kephart, W. C., Mumford, P. W., Mao, X., Romero, M. A., Hyatt, H. W., Zhang, Y., ... Roberts, M. D. (2017). 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, 9(9), doi:10.3390/nu9091019.
Kephart WC, et al. 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 Sep 15;9(9) PubMed PMID: 28914762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kephart,Wesley C, AU - Mumford,Petey W, AU - Mao,Xuansong, AU - Romero,Matthew A, AU - Hyatt,Hayden W, AU - Zhang,Yufeng, AU - Mobley,Christopher B, AU - Quindry,John C, AU - Young,Kaelin C, AU - Beck,Darren T, AU - Martin,Jeffrey S, AU - McCullough,Danielle J, AU - D'Agostino,Dominic P, AU - Lowery,Ryan P, AU - Wilson,Jacob M, AU - Kavazis,Andreas N, AU - Roberts,Michael D, Y1 - 2017/09/15/ PY - 2017/08/28/received PY - 2017/09/11/revised PY - 2017/09/13/accepted PY - 2017/9/16/entrez PY - 2017/9/16/pubmed PY - 2018/6/14/medline KW - brain KW - ketogenic dieting KW - ketone salts KW - liver KW - mitochondria KW - oxidative stress KW - skeletal muscle JF - Nutrients JO - Nutrients VL - 9 IS - 9 N2 - 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. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/28914762/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_ L2 - http://www.mdpi.com/resolver?pii=nu9091019 DB - PRIME DP - Unbound Medicine ER -