Abstract
Ketogenic diets (KD) that are very high in fat and low in carbohydrates are thought to simulate the metabolic effects of starvation. We fed mice with a KD for seven days to assess the underlying mechanisms of muscle wasting induced by chronic starvation. This diet decreased the weight of the gastrocnemius (Ga), tibialis anterior (TA) and soleus (Sol) muscles by 23%, 11% and 16%, respectively. The size of Ga, TA, Sol muscle fibers and the grip strength of four limbs also significantly declined by 20%, 28%, 16% and 22%, respectively. The muscle atrophy-related genes Mafbx, Murf1, Foxo3, Lc3b and Klf15 were upregulated in the skeletal muscles of mice fed with the KD. In accordance with the reduced expression of anabolic genes such as Igf1, surface sensing of translation (SUnSET) analyses of fast-twitch Ga, TA and Sol muscles revealed that the KD suppressed muscle protein synthesis. The mRNA expression of oxidative stress-responsive genes such as Sod1 was significantly increased in all muscles examined. In addition to hypercorticosteronemia, hypoinsulinemia and reduced IGF-1, oxidative stress might also be involved in KD-induced muscle atrophy. Feeding mice with a KD is a novel experimental animal model of muscle-wasting induced by chronic starvation.
Highlights
Ketogenic diets (KD) that are very high in fat and low in carbohydrates are thought to simulate the metabolic effects of starvation
We compared energy metabolism in the skeletal muscles of mice fed with the KD and the normal diet (ND) by measuring activities of pyruvate dehydrogenase (PDH), which catalyzes the oxidative decarboxylation of pyruvate into acetyl-CoA and links glycolysis to the citric acid cycle
The expression of pyruvate dehydrogenase kinase 4 (Pdk4) that contributes to PDH phosphorylation and impaired glucose utilization, was increased 2.2, 2.8- and 3.8-fold in the Ga, tibialis anterior (TA) and Sol muscles, respectively, of mice fed with the KD, compared with the ND (Fig. 4a)
Summary
Ketogenic diets (KD) that are very high in fat and low in carbohydrates are thought to simulate the metabolic effects of starvation. We fed mice with a KD for seven days to assess the underlying mechanisms of muscle wasting induced by chronic starvation This diet decreased the weight of the gastrocnemius (Ga), tibialis anterior (TA) and soleus (Sol) muscles by 23%, 11% and 16%, respectively. Activation of these muscle atrophy-related genes is regulated by GC-regulated transcription factors such as glucocorticoid receptor (GR)[8,10,12], FOXOs11 and KLF1513 These molecular events might be transient in rodents that have fasted for 24–48 h and might not accurately reflect the effects of chronically poor (a). Ketogenic diets (KD) comprising high-fat, low-carbohydrate and protein contents have been included in weight loss strategies for both obese and non-obese individuals Such diets mimic the metabolic status of fasting or caloric restriction and are based on theoretical concepts of the effects of dietary component ratios on energy expenditure[15]. The present study aimed to determine degrees of muscle atrophy in mice fed with a KD
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
