Changes in hepatic L-carnitine levels in people with metabolic dysfunction-associated steatotic liver disease (MASLD) assessed by magnetic resonance techniques

Abstract L-carnitine is critical for metabolism of some fatty acids therefore different carnitine species may play a role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis. Until recently, hepatic acetylcarnitine could not be quantified non-invasively. Now new technical developments in magnetic resonance spectroscopy (MRS) enable quantification of hepatic acetylcarnitine content in vivo. The aim of this study was to evaluate potential metabolic changes in healthy volunteers and patients with different stages of MASLD before and after a single injection of L-carnitine. This prospective study recruited 10 healthy volunteers and 17 patients (11 with low-risk MASLD, 6 with high-risk MASLD) who underwent cardiac and hepatic MRI and MRS for hepatic acetylcarnitine quantification at baseline and 2 h after injecting 50 mg/kg body weight L-carnitine. Serum samples were obtained for biomarker measurement. A single injection of L-carnitine significantly elevated hepatic acetylcarnitine levels in healthy volunteers (Δ ACC = 0.172, p = 0.038) and low-risk MASLD (Δ ACC = 1.677, p = 0.043), but not in high-risk MASLD (Δ ACC =-0.144, p = 0.397). However, high-risk MASLD showed elevated hepatic acetylcarnitine at baseline (Δ ACC = 0.58, p = 0.007), whereas variability in low-risk MASLD masked differences vs. healthy volunteers. At baseline, serum medium-chain carnitine species were higher in the high-risk MASLD group (0.88 ± 0.28µmol/L, p = 0.002) and low-risk MASLD group (0.77 ± 0.49µmol/L, p = 0.03) compared to healthy volunteers (0.36 ± 0.23µmol/L). We showed for the first time that acetylcarnitine can be evaluated in vivo in patients with different stages of MASLD. The divergent hepatic responses to L-carnitine suggest stage-dependent differences in hepatic metabolic response that may reflect disease severity, potentially arising from differences in metabolic flexibility, carnitine transport, mitochondrial function, or baseline saturation of hepatic acetylcarnitine. Further studies are needed to confirm whether hepatic or circulating acetylcarnitine levels could serve as early biomarkers of MASLD progression.