Effects of Ketogenic Diet on p70S6k Phosphorylation in Young Adult and Old Soleus Muscle

Abstract

A ketogenic diet (KD) has been proposed as a treatment for many conditions including obesity, diabetes, epilepsy, and Parkinson's Disease. Various studies have shown its effects on health and lifespan in model organisms suggesting that it is beneficial for many individuals. Some concern exists that KD might negatively impact anabolic signaling through the mTOR pathway, but the molecular signaling effects of the diet remain largely unexplored, particularly in skeletal muscle. The purpose of this study, therefore, was to determine how KD affects downstream mTOR signaling in skeletal muscle from young and old rats. Young adult (YA; 5 mo.) and old (O; 28 mo.) male Fisher 344 rats were isocalorically fed either a ketogenic diet (KD; Envigo Teklad Custom Diet, TD.10911; 22.4% protein, 77.1% fat, 0.5% carbohydrates) or standard diet (STD; Envigo Teklad Rodent Diet, 8604; 32% protein, 14% fat, 54% carbohydrate) for four weeks. Soleus muscles were harvested and assessed for muscle size and effects on p70 ribosomal protein S6 kinase (S6k) phosphorylation. Soleus muscles from YA KD rats were ~11% smaller than for corresponding YA STD rats, and O KD soleus muscles were ~6% larger vs. O STD muscles, though neither of these differences were significant. Phosphorylation of S6k was significantly (p < 0.05) decreased 75% in YA KD vs. YA STD. S6k phosphorylation was reduced 88% in O muscles, but, in contrast to the YA muscles, was increased by ~400% by KD vs. STD in O muscles. Based on this evidence, we conclude that in slow‐twitch soleus muscles, administration of KD can decrease skeletal muscle mTOR signaling in YA muscles and increase its signaling in O muscles.Support or Funding InformationThis work was supported by a Brigham Young University Gerontology Program award.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A review of the uses of the ketogenic diet

“…Adherence to the ketogenic diet (KD) increases life expectancy, improves health, acts as a neuroprotectant, improves mitochondrial function, activates autophagy, has antiinflammatory effects, and increases expression of antioxidants and anabolic signals in aged mice [55], [56], [57]. A study (Wallace et al, 2021) compared the muscles of mice fed a ketogenic diet for 14 months.…”