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Effect of Betaine on Liver Tissue and Ultrastructural Changes in Methionine–Choline Deficient Diet-Induced NAFLD by M Vesković, M Labudović-Borović, D Mladenović, J Jadžić, B Jorgačević, D Vukićević, D Vučević, and T Radosavljević, Microsc Microanal | doi:10.1017/S14319227620024265
A methionine–choline-deficient (MCD) diet is widely used for
the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in animal models ( Figure). Te histopathological identification of NASH involves steatosis, hepatocellular injury in the form of ballooning predominantly located in acinar zone 3, lobular inflammation, and perisinusoidal fibrosis due to collagen deposition in the space of Disse. Ultrastruc- tural modification of hepatocytes such as changes in the number of autophagosomes or changes in mitochondrial structure and nuclear chromatin may represent important early signs of altered hepatocel- lular function. Betaine reduces the degree of steatosis and inflam- mation and the size of mitochondria in MCD-induced NAFLD potentially by its antioxidant and anti-apoptotic effects. Betaine also stimulates autophagy by the activation of the Akt/mTOR signaling pathway with an increase in the number of hepatocyte autophago- somes. Induction of lipophagy in NAFLD may lead to the removal of accumulated lipids from hepatocytes that may represent an addi- tional hepatoprotective mechanism of betaine.
Effects of betaine on liver ultrastructural changes in the MCD group in mice with NAFLD. Extensive microvesicular fatty change; numerous hepatic stellate cells/ myofibroblasts (white arrowheads). Bar = 20 µm.
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