Ketogenic diet preserves muscle mass and strength in a mouse model of type 2 diabetes

PLoS One. 2024 Jan 10;19(1):e0296651. doi: 10.1371/journal.pone.0296651. eCollection 2024.

Abstract

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.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental*
  • Diabetes Mellitus, Type 2*
  • Diet, Ketogenic*
  • Disease Models, Animal
  • Inflammasomes
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal
  • NLR Family, Pyrin Domain-Containing 3 Protein

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes

Grants and funding

This work was supported by research grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (NRF-2020R1F1A1065326 and NRF-2022R1F1A1062867), and a research grant (2023-0251) from Seoul Women's University. The funder had no role in study design, data collection, analysis and interpretation, the decision to publish, or manuscript preparation.