Fig 3 -

The effects of a ketogenic diet (KD) on (a) gastrocnemius (GA) muscle morphology, (b) cross-sectional areas (CSA) and (c) Minimal Feret’s Diameter of GA muscle fiber, and (d) distribution of CSA of GA muscle fiber. (a) Representative photographs of hematoxylin and eosin (H&E)-stained GA muscle sections. Original magnification, 400x. Scale bar, 50 μm. Data are expressed as means ± SEM (n = 4 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. CON, control; DM, diabetes.</p

Primer sequences for real-time reverse transcription polymerase chain reaction.

Primer sequences for real-time reverse transcription polymerase chain reaction.</p

Fig 4 -

The effects of a ketogenic diet (KD) on muscle strength: (a) forelimb, (b) hindlimb, and (c) wholelimb grip strengths. Data are expressed as means ± SEM (n = 10 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. BW, body weight; CON, control; DM, diabetes.</p

Diagram of experimental procedure.

The mice of a ketogenic diet (KD) group were fed a KD from experimental week 8 for 6 weeks. CON, control; DM, diabetes melitus; NAM, nicotinamide; STZ, streptozotocin.</p

Diet composition.

Diabetes is often associated with reduced muscle mass and function. The ketogenic diet (KD) may improve muscle mass and function via the induction of nutritional ketosis. To test whether the KD is able to preserve muscle mass and strength in a mouse model of type 2 diabetes (T2DM), C57BL/6J mice were assigned to lean control, diabetes control, and KD groups. The mice were fed a standard diet (10% kcal from fat) or a high-fat diet (HFD) (60% kcal from fat). The diabetic condition was induced by a single injection of streptozotocin (STZ; 100 mg/kg) and nicotinamide (NAM; 120 mg/kg) into HFD-fed mice. After 8-week HFD feeding, the KD (90% kcal from fat) was fed to the KD group for the following 6 weeks. After the 14-week experimental period, an oral glucose tolerance test and grip strength test were conducted. Type 2 diabetic condition induced by HFD feeding and STZ/NAM injection resulted in reduced muscle mass and grip strength, and smaller muscle fiber areas. The KD nutritional intervention improved these effects. Additionally, the KD altered the gene expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in the muscles of diabetic mice. Collectively, KD improved muscle mass and function with alterations in NLRP3 inflammasome and ER stress.</div

Body weight (BW) changes, food intake, and muscle tissue weights in the ketogenic diet (KD)-fed mice.

Body weight (BW) changes, food intake, and muscle tissue weights in the ketogenic diet (KD)-fed mice.</p

The effects of a ketogenic diet (KD) on nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome- and endoplasmic reticulum (ER) stress-related markers in gastrocnemius (GA) muscles.

Gene expression of (a) NLRP3, (b) apoptosis-associated speck-like protein (ASC), (c) protein kinase RNA-like endoplasmic reticulum kinase (Perk), (d) eukaryotic translation initiation factor 2 alpha (eIF2 alpha), (e) inositol-requiring enzyme 1 (Ire1), (f) Akt, (g) mammalian target of rapamycin (mTOR), and (h) forkhead box O1 (Foxo1) in GA muscles. Data are expressed as means ± SEM (n = 10 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. CON, control; DM, diabetes.</p

Fig 2 -

The effects of a ketogenic diet (KD) on serum concentrations of (a) corticosterone, (b) free fatty acids, (c) albumin, (d) insulin-like growth factor-1 (IGF-1), and (e) C-peptide, and pyruvate dehydrogenase (PDH) activity and acetyl-CoA concentration in gastrocnemius (GA) muscles. Data are expressed as means ± SEM (n = 10 per group). One-way analysis of variance with Bonferroni post-hoc analysis was used to compare the differences in outcome variables between groups. * p † p < 0.05 vs. DM group. CON, control; DM, diabetes.</p

The effects of a ketogenic diet (KD) on fasting serum glucose, the area under the curve (AUC) of oral glucose tolerance test (OGTT), fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and serum beta-hydroxybutyrate (BHB) concentrations in diabetic mice.

The effects of a ketogenic diet (KD) on fasting serum glucose, the area under the curve (AUC) of oral glucose tolerance test (OGTT), fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and serum beta-hydroxybutyrate (BHB) concentrations in diabetic mice.</p