The Influence of Trehalose on Atherosclerosis and Hepatic Steatosis in Apolipoprotein E Knockout Mice

Abstract

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, according to the literature, its anti-atherosclerotic and anti-steatotic potential seem to depend on the experimental setting. The aim of our study was to comprehensively describe the influence of a prolonged treatment with orally administered trehalose on the development of atherosclerotic lesions and hepatic steatosis in apolipoprotein E knockout (apoE−/−) mice in an experimental set up reflecting both moderate and severe proatherogenic conditions: male apoE−/− mice on a chow diet (CD) and female apoE−/− mice fed with a high-fat diet (HFD). We found that exogenous trehalose inhibited atherosclerosis and attenuated hepatic steatosis in apoE−/− mice. Such effects of trehalose were not associated with changes of plasma cholesterol, low-density lipoproteins (LDL), or high-density lipoproteins (HDL). Moreover, the anti-steatotic action of trehalose in the liver was associated with the induction of autophagy. The exact molecular mechanisms of both the anti-atherosclerotic action of trehalose and its inhibitory effect on liver steatosis require further clarification.

The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE–Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype

“…The assessment was performed using Oil Red O and HE staining (O0625, lot. 093k3650, Sigma-Aldrich, St. Louis, MO) [ 25 ]. Immunohistochemistry for all macrophages and smooth muscles as well as polarization of macrophages was performed as described previously [ 14 ].…”

Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis

“…Apolipoprotein E (ApoE) is a lipid carrier and can remove lipoproteins in arteries with an antiatherosclerosis activity [25]. ApoE-knockout mice fed with a high-fat diet (HFD) show features of atherosclerosis with high serum lipid levels and have been considered as an ideal model for studying atherosclerosis [26]. Therefore, in the current study, we used ApoE-knockout mice on a high-fat diet to establish an atherosclerosis model.…”

Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis

“…The development of atherosclerotic lesions in apoE −/− mice was evaluated using cross-section method, as described before [ 48 ]. The aortic sections (10-μm thickness) were stained with Oil Red-O (Sigma-Aldrich, St. Louis, MO, USA) to measure the area of atherosclerotic plaques.…”

“…Sections of ascending aorta were fixed in acetone and used for immunohistochemistry, as described previously [ 48 ]. To detect the content of macrophages and smooth muscles cells in atherosclerotic plaques, the sections were stained with primary antibodies against CD68 (Serotec, Kidlington, UK) (dilution 1:800) and smooth muscle α-actin (SMA) (Sigma-Aldrich, St. Louis, MO, USA) (dilution 1:800), respectively.…”