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Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats.

Abstract

Ketogenic diets (KD) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise are unknown. We investigated the effects of a KD vs a 'Western' diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to three groups (n= 8-14 per group): standard chow (SC; 17% Fat), WD (42% Fat) or KD (90.5% Fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD vs SC, although KD females displayed lower BF% vs WD (p≤0.05). Liver triglycerides were higher in KD and WD vs SC, but were attenuated in KD females vs WD (p≤0.05). KD suppressed hepatic markers of de novo lipogenesis (FAS, ACC) and increased markers of mitochondrial biogenesis/content (PGC-1α, TFAM and citrate synthase activity). KD also increased the hepatic GPx1 and lowered oxidized glutathione. Females rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (LC3II/I ratio, ATG 12:5) and cellular energy homeostasis (pAMPK/AMPK) vs males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation. • Ketogenic diet feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, increased markers of mitochondrial content vs western diet feeding. • Males and females responded similarly to combined ketogenic diet feeding and exercise. • Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats.

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  • Authors+Show Affiliations

    ,

    Harry S Truman Memorial Veterans Medical Center, Research Service, Columbia, Missouri, United States. University of Missouri, Department of Nutrition and Exercise Physiology, Columbia, Missouri, United States ; mpmxn5@mail.missouri.edu.

    ,

    Harry S Truman Memorial Veterans Medical Center, Research Service, Columbia, Missouri, United States. University of Missouri, Department of Nutrition and Exercise Physiology, Columbia, Missouri, United States ; rcw4b@mail.missouri.edu.

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    University of Missouri, Department of Biomedical Sciences, Columbia, Missouri, United States ; taylor.kelty@mail.missouri.edu.

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    Harry S Truman Memorial Veterans Medical Center, Research Service, Columbia, Missouri, United States. University of Missouri, Department of Nutrition and Exercise Physiology, Columbia, Missouri, United States. University of Missouri, Medicine-Division of Gastroenterology and Hepatology, Columbia, Missouri, United States ; lrb5z5@mail.missouri.edu.

    ,

    Harry S Truman Memorial Veterans Medical Center, Research Service, Columbia, Missouri, United States. University of Missouri, Department of Nutrition and Exercise Physiology, Columbia, Missouri, United States ; nynb5b@mail.missouri.edu.

    ,

    University of Missouri , Department of Biomedical Sciences , 1600 East Rollins , Columbia, Missouri, United States , 65211 ; boothf@missouri.edu.

    Harry S Truman Memorial Veterans Medical Center, Research Service, Columbia, Missouri, United States. University of Missouri, Department of Nutrition and Exercise Physiology, Columbia, Missouri, United States. University of Missouri, Medicine-Division of Gastroenterology and Hepatology, Columbia, Missouri, United States ; RectorS@health.missouri.edu.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31116955

    Citation

    Moore, Mary Patricia, et al. "Ketogenic Diet in Combination With Voluntary Exercise Impacts Markers of Hepatic Metabolism and Oxidative Stress in Male and Female Wistar Rats." Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquee, Nutrition Et Metabolisme, 2019.
    Moore MP, Cunningham RP, Kelty TJ, et al. Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats. Appl Physiol Nutr Metab. 2019.
    Moore, M. P., Cunningham, R. P., Kelty, T. J., Boccardi, L. R., Nguyen, N. Y., Booth, F. W., & Rector, R. S. (2019). Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats. Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquee, Nutrition Et Metabolisme, doi:10.1139/apnm-2019-0042.
    Moore MP, et al. Ketogenic Diet in Combination With Voluntary Exercise Impacts Markers of Hepatic Metabolism and Oxidative Stress in Male and Female Wistar Rats. Appl Physiol Nutr Metab. 2019 May 22; PubMed PMID: 31116955.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats. AU - Moore,Mary Patricia, AU - Cunningham,Rory P, AU - Kelty,Taylor J, AU - Boccardi,Luigi R, AU - Nguyen,Nhu Y, AU - Booth,Frank W, AU - Rector,R Scott, Y1 - 2019/05/22/ PY - 2019/5/23/entrez PY - 2019/5/23/pubmed PY - 2019/5/23/medline JF - Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme JO - Appl Physiol Nutr Metab N2 - Ketogenic diets (KD) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise are unknown. We investigated the effects of a KD vs a 'Western' diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to three groups (n= 8-14 per group): standard chow (SC; 17% Fat), WD (42% Fat) or KD (90.5% Fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD vs SC, although KD females displayed lower BF% vs WD (p≤0.05). Liver triglycerides were higher in KD and WD vs SC, but were attenuated in KD females vs WD (p≤0.05). KD suppressed hepatic markers of de novo lipogenesis (FAS, ACC) and increased markers of mitochondrial biogenesis/content (PGC-1α, TFAM and citrate synthase activity). KD also increased the hepatic GPx1 and lowered oxidized glutathione. Females rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (LC3II/I ratio, ATG 12:5) and cellular energy homeostasis (pAMPK/AMPK) vs males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation. • Ketogenic diet feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, increased markers of mitochondrial content vs western diet feeding. • Males and females responded similarly to combined ketogenic diet feeding and exercise. • Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats. SN - 1715-5320 UR - https://www.unboundmedicine.com/medline/citation/31116955/Ketogenic_diet_in_combination_with_voluntary_exercise_impacts_markers_of_hepatic_metabolism_and_oxidative_stress_in_male_and_female_Wistar_rats L2 - http://www.nrcresearchpress.com/doi/full/10.1139/apnm-2019-0042?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -