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Transcriptomic Profiles Reflect Dietary Differences in Skeletal Muscle between Keto-Adapted and High Carbohydrate Elite Ultra Endurance Athletes

SAENZ, CATHERINE
http://rave.ohiolink.edu/etdc/view?acc_num=osu1468950872

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Kinesiology.
Keto-adaptation leads to a consistent phenotype characterized by augmented ketogenesis and lipid oxidation at rest and during submaximal exercise. There are no published research studies examining underlying gene expression patterns of keto-adapted athletes in skeletal muscle, the primary site of ATP production during exercise. The purpose of this dissertation is to compare global skeletal muscle gene expression patterns in ultra endurance athletes habitually consuming a very low-carbohydrate `ketogenic’ diet (LCD) versus a traditional, high-carbohydrate diet (HCD). LCD athletes were hypothesized to have increased levels of mRNA expression in genes that relate to the keto-adapted phenotype such as increased fat oxidation, decreased utilization of carbohydrate, and accelerated ketogenesis. 20 elite ultra-endurance athletes (men, age 33.5 ± 6.4 yr, BMI 22.6 ± 3.3 kg/m2, VO2max 64.5 ± 4.9 mL/kg/min) habitually consuming a HCD (n=10; 58% CHO, 15% PRO, 28% FAT) or a LCD (n=10; 11% CHO, 19% PRO, 71% FAT) for a minimum of 6 consecutive months were matched for age, exercise training, and competition events. Muscle biopsies from the vastus lateralis were obtained at rest (BL), immediately post (IP) and 120 minutes after (120+) a 180 minute treadmill run at 64% VO2max. cDNA library was prepared from total RNA and sequenced for whole transcriptome. Reads per kilobase of transcripts per million were used to compare gene expression between groups at BL, IP, and 120+ (p = 0.01; false discovery rate (FDR) = 0.05). Genes significantly different between groups were further analyzed for magnitude of difference (± 1.5 fold change) and pattern and functional characterization through heat map visualization, functional annotations, and gene ontology (p<0.05, FDR <0.1). A linear regression model was used to compare highly significant genes to rate of fat oxidation at BL, IP, and 120+. LCD athletes consumed a ketogenic diet for an average of 20 months (9-36mo). A total of 25, 262 genes were sequenced, with 653 genes significantly different between HCD and LCD athletes (p <0.01). LCD group revealed upregulated gene expression in 26 genes at BL, 27 genes at IP, and one gene at +120. Genes affected by LCD were predominantly located in the mitochondria. A select group of genes involved in lipid and ketone metabolism were markedly upregulated in LCD athletes such as H1FX, HMGCS2, HADHA, and ASS1 at BL and IP. PPP1R1A, involved in glycogen metabolism, was the only gene significantly different between groups at all time points. HADHA was significantly correlated to whole body fat oxidation at BL, explaining 46% of the variance (ß = 0.678, p= 0.05). Contrary to the HCD group, genes involved in lipid and ketone metabolism were upregulated in LCD athletes. Unexpectedly, one gene involved in glycogen metabolism was significantly upregulated at all time points in LCD athletes. These results indicate that habitual ingestion of a ketogenic diet leads to chronic changes in constitutive skeletal muscle gene expression at rest and surrounding a bout of exercise. These gene expression patterns support the keto-adapted phenotype of accelerated ketogenesis and increased capacity for fat oxidation.
Jeff Volek (Advisor)
129 p.
Kinesiology; Nutrition
Ketogenic diets, Ketoadaptation, Ultra endurance exercise, Elite athletes, Low carbohydrate diets, High carbohydrate diets, Ultra marathoners

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Citations

  • SAENZ, C. (2016). Transcriptomic Profiles Reflect Dietary Differences in Skeletal Muscle between Keto-Adapted and High Carbohydrate Elite Ultra Endurance Athletes [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468950872

    APA Style (7th edition)

  • SAENZ, CATHERINE. Transcriptomic Profiles Reflect Dietary Differences in Skeletal Muscle between Keto-Adapted and High Carbohydrate Elite Ultra Endurance Athletes . 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1468950872.

    MLA Style (8th edition)

  • SAENZ, CATHERINE. "Transcriptomic Profiles Reflect Dietary Differences in Skeletal Muscle between Keto-Adapted and High Carbohydrate Elite Ultra Endurance Athletes ." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468950872

    Chicago Manual of Style (17th edition)

osu1468950872
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This open access ETD is published by The Ohio State University and OhioLINK.