L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disorder. NAFLD, associated lipotoxicity, fibrosis, oxidative stress, and altered mitochondrial metabolism, is responsible for systemic inflammation, which contributes to organ dysfunction in extrahepatic tissues, including the heart. We investigated the ability of L-carnitine (LC) to oppose the pathogenic mechanisms underlying NAFLD progression and associated heart dysfunction, in a mouse model of methionine-choline-deficient diet (MCDD). Mice were divided into three groups: namely, the control group (CONTR) fed with a regular diet and two groups fed with MCDD for 6 weeks. In the last 3 weeks, one of the MCDD groups received LC (200 mg/kg each day) through drinking water (MCDD + LC). The hepatic lipid accumulation and oxidative stress decreased after LC supplementation, which also reduced hepatic fibrosis via modulation of ␣-smooth muscle actin (␣SMA), peroxisome-activated receptor gamma (PPAR␥), and nuclear factor kappa B (Nf B) expression. LC ameliorated systemic inflammation, mitigated cardiac reactive oxygen species (ROS) production, and prevented fibrosis progression by acting on signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1-2 (ERK1-2), and ␣SMA. This study confirms the existence of a relationship between fatty liver disease and cardiac abnormalities and highlights the role of LC in controlling liver oxidative stress, steatosis, fibrosis, and NAFLD-associated cardiac dysfunction.

Effects of L-Carnitine Supplementation on MicroRNA-217 Expression Level in Non-alcoholic Steatohepatitis Suffering Patients with Obesity: A Randomized Controlled Trial

“…Further, the results of our study were consistent to previous studies reported bene cial effects of Lcarnitine supplementation on oxidative stress, NAFLD/NASH, and liver brosis 10,16,17 . According to previous studies, a major cause of fat accumulation and oxidative stress exacerbation in hepatic tissue, is inhibition of mitochondrial fatty acid oxidation which may be modi ed by L-carnitine supplementation 17, 18 .…”

Differences among patients with and without nonalcoholic fatty liver disease having elevated alanine aminotransferase levels at various stages of metabolic syndrome

“…Acetyl-L-carnitine is an acetylated derivative of L-carnitine that participates in oxidative metabolism. Decreased L-carnitine levels were associated with insulin resistance and L-carnitine supplementation in rats and mice improved metabolic function and NAFLD [50,51]. Our findings suggest that lower levels of acetyl-L-carnitine may be associated with NAFLD.…”

PPARγ/NF‐κB and TGF‐β1/Smad pathway are involved in the anti‐fibrotic effects of levo‐tetrahydropalmatine on liver fibrosis

“…More importantly, the inhibitory effect of curcumin on NF‐κB trans‐activating activity could be reversed by a specific PPARγ antagonist PD‐68235 in a dose‐dependent manner 33 . In a mice NAFLD model, L‐carnitine alleviated hepatic inflammation and fibrosis by inhibiting NF‐κB p65 in a PPARγ‐dependent manner 58 . Hepatic macrophages, or Kupffer cells, are an important source of ECM, TGF‐β1 and other inflammatory cytokines in liver fibrosis 59 .…”