Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats

Abstract

BackgroundRecently, it has been shown that carnitine down-regulates genes involved in the ubiquitin-proteasome system (UPS) in muscle of pigs and rats. The mechanisms underlying this observation are yet unknown. Based on the previous finding that carnitine increases plasma IGF-1 concentration, we investigated the hypothesis that carnitine down-regulates genes of the UPS by modulation of the of the IGF-1/PI3K/Akt signalling pathway which is an important regulator of UPS activity in muscle.MethodsMale Sprague–Dawley rats, aged four weeks, were fed either a control diet with a low native carnitine concentration or the same diet supplemented with carnitine (1250 mg/kg diet) for four weeks. Components of the UPS and IGF-1/PI3K/Akt signalling pathway in skeletal muscle were examined.ResultsRats fed the diet supplemented with carnitine had lower mRNA and protein levels of MuRF1, the most important E3 ubiquitin ligase in muscle, decreased concentrations of ubiquitin-protein conjugates in skeletal muscle and higher IGF-1 concentration in plasma than control rats (P < 0.05). Moreover, in skeletal muscle of rats fed the diet supplemented with carnitine there was an activation of the PI3K/Akt signalling pathway, as indicated by increased protein levels of phosphorylated (activated) Akt1 (P < 0.05).ConclusionThe present study shows that supplementation of carnitine markedly decreases the expression of MuRF1 and concentrations of ubiquitinated proteins in skeletal muscle of rats, indicating a diminished degradation of myofibrillar proteins by the UPS. The study moreover shows that supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway which in turn might contribute to the observed down-regulation of MuRF1 and muscle protein ubiquitination.

L-carnitine affects osteoblast differentiation in NIH3T3 fibroblasts by the IGF-1/PI3K/Akt signalling pathway

“…Some studies suggest that LC promoted osteoblast proliferation and differentiation in vitro (43,44), while other studies indicated that LC inhibited proliferation in VSMCs (45). In this study, we found that the 10 μM LC positively affected osteoblast proliferation, but the higher concentration of LC (100 μM) slightly decreased osteoblast proliferation compared with the control.…”

Potential therapeutic interventions for chronic kidney disease‐associated sarcopenia via indoxyl sulfate‐induced mitochondrial dysfunction

“…In mice that are fed a high‐fructose diet which is known as an acquired model of insulin resistance, the presence of L‐carnitine reduced protein oxidation in the lens, and the decreased anti‐oxidative enzymes were recovered, thus preserving mitochondrial function 30. Moreover, the presence of L‐carnitine increases Akt phosphorylation and accelerates myotube formation in C2C12 cells31 and in the muscle of rats 32. These pleiotropic effects of L‐carnitine, including anti‐oxidative and anti‐inflammatory activities and maintaining Akt signaling, could play an important role in the protection of mitochondrial function in CKD conditions, especially in cases of higher IS accumulation, such as uremia.…”

Effect of L-carnitine and Hoodia gordonii Supplementation on Metabolic Markers and Physical Performance under Short Term Calorie Restriction in Rats

“…It is speculated that the rise of IGF-1 levels,though statistically not significant (Table 1) in the treated rats is attributed to L-carnitine supplementation since no change in insulin was observed. Studies have confirmed that carnitine supplementation causes an increase in IGf-1 levels in rats, pigs, chickens and humans 55 . Since IGf-1 also has hypoglycemic effects, the decrease in blood glucose levels of CR+CAR+HG could be related to the increase in plasma IGf-1.…”