**2.1. Hepatocellular uptake of vitamin E**

Vitamin E is absorbed in the intestine along with lipids (for details, see [8]) and is packed into lipoproteins. These are transported via lymph or blood toward the liver (via chylomicron remnants, low density lipoproteins (LDL), and high density lipoproteins (HDL) [10, 11]). Different mechanisms facilitate the cellular uptake of vitamin E: (i) via lipid transfer proteins or lipases, (ii) receptor-mediated lipoprotein endocytosis, and (iii) selective lipid uptake [12]. The degradation of chylomicrons to chylomicron remnants by lipoprotein lipase (LPL) seems to be highly important for vitamin E uptake in the liver; when lipolysis of triglyceride-rich chylomicrons by LPL is inhibited, the α-TOH uptake in the liver is diminished [13]. The phospholipid transfer protein (PLTP) mediates the exchange of phospholipids between lipoproteins [14] and is also able to bind α-TOH *in vitro* [15]. PLTP-null mice have lower hepatic levels of vitamin E than the wild-type mice [16]; hence, the transfer of vitamin E between the lipoproteins seems to be important for its effective hepatic uptake. The chylomicron remnants and LDL are taken up by the liver via endocytosis, mainly mediated through the LDL receptor (LDLR) or LDLR-related proteins [6, 17]. In addition, the cholesterol transporter Niemann-Pick C1-like 1 (NPC1L1) is involved in hepatic vitamin E uptake; α-TOH binds to the N-terminal domain of NPC1L1, which mediates α-TOH uptake via endocytosis (mechanism similar to intestinal cholesterol uptake) [18]. The scavenger receptor B type I (SR-BI) is known to mediate the uptake of vitamin E in several tissues (e.g., intestine [19], epithelium [20], and hepatocytes [21]) by channeling the molecules into the cells (shown for cholesterol or triglycerides [22]). Furthermore, the scavenger receptor cluster of differentiation 36 (CD36) is likely involved in hepatic uptake of vitamin E [23].
