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. 2020 Oct 30;15(10):e0241382.
doi: 10.1371/journal.pone.0241382. eCollection 2020.

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats

Yuji Ogura  1 , Chiaki Kakehashi  1 , Toshinori Yoshihara  2 , Mitsutoshi Kurosaka  1 , Ryo Kakigi  3 , Kazuhiko Higashida  4 , Sei-Etsu Fujiwara  1 , Tatsuo Akema  1 , Toshiya Funabashi  1
Affiliations

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats

Yuji Ogura et al. PLoS One. .

Abstract

Recent studies of the ketogenic diet, an extremely high-fat diet with extremely low carbohydrates, suggest that it changes the energy metabolism properties of skeletal muscle. However, ketogenic diet effects on muscle metabolic characteristics are diverse and sometimes countervailing. Furthermore, ketogenic diet effects on skeletal muscle performance are unknown. After male Wistar rats (8 weeks of age) were assigned randomly to a control group (CON) and a ketogenic diet group (KD), they were fed for 4 weeks respectively with a control diet (10% fat, 10% protein, 80% carbohydrate) and a ketogenic diet (90% fat, 10% protein, 0% carbohydrate). After the 4-week feeding period, the extensor digitorum longus (EDL) muscle was evaluated ex vivo for twitch force, tetanic force, and fatigue. We also analyzed the myosin heavy chain composition, protein expression of metabolic enzymes and regulatory factors, and citrate synthase activity. No significant difference was found between CON and KD in twitch or tetanic forces or muscle fatigue. However, the KD citrate synthase activity and the protein expression of Sema3A, citrate synthase, succinate dehydrogenase, cytochrome c oxidase subunit 4, and 3-hydroxyacyl-CoA dehydrogenase were significantly higher than those of CON. Moreover, a myosin heavy chain shift occurred from type IIb to IIx in KD. These results demonstrated that the 4-week ketogenic diet improves skeletal muscle aerobic capacity without obstructing muscle contractile function in sedentary male rats and suggest involvement of Sema3A in the myosin heavy chain shift of EDL muscle.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Change in body mass during the experimental period in CON (n = 16) and KD (n = 16).
* Significant difference was found between CON and KD. Values are expressed as means ± S.E.M.
Fig 2
Fig 2. Protein expression of metabolic enzymes in CON (n = 5) and KD (n = 5).
Representative images of the protein band and transferred protein of PFK (A), CS (B), SDH (C), COX-IV (D), and HAD (E). Protein expressions of PFK (F), CS (G), SDH (H), COX-IV (I), and HAD (J). * Significant difference was found between CON and KD. Values are expressed as means ± S.E.M.
Fig 3
Fig 3. Proportion and the protein expression of MyHC isoforms in CON (n = 5) and KD (n = 5).
(A) A representative image of the separation. Soleus was used for a reference of type I isoform. (B) Relative proportion of MyHC isoforms presented with representative images of the protein band and transferred protein of MyHC type IIa (C), IId (D), and IIb (E). Protein expressions of MyHC type IIa (F), IId (G), and IIb (H). * Significant difference was found between CON and KD. Values are expressed as means ± S.E.M.
Fig 4
Fig 4. Protein expression of PGC-1α, PPAR-α, and Mef2C in CON (n = 5) and KD (n = 5).
Representative images of the protein band and transferred protein of PGC-1α (A), PPAR-α (B), and Mef2C (C). Protein expressions of PGC-1α (D), PPAR-α (E), and Mef2C (F). Values are expressed as means ± S.E.M.
Fig 5
Fig 5. Protein expression of Sema3A in CON (n = 5) and KD (n = 5).
Representative images of the protein band and transferred protein (A) The protein expression of Sema3A (B). *Significant difference was found between CON and KD. Values are expressed as means ± S.E.M.
Fig 6
Fig 6. Muscle force of CON and KD.
(A) Twitch tension of CON (n = 6) and KD (n = 5). Values are expressed as means ± S.E.M. (B) Tetanic tension under stimulation at 90 Hz, 300 ms duration in CON (n = 6) and KD (n = 5). Values are expressed as means ± S.E.M. (C) Fatigue experiment of CON (n = 5) and KD (n = 5). A main effect of time was found (p < .001). Values are expressed as means ± S.E.M.
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Grants and funding

This study was supported by a Grant-in-Aid for Exploratory Research (24650334 to CK) and by a Grant-in-Aid for Scientific Research (18K17767 to CK) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT).
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