**Acknowledgements**

*3.4.3. Disorders of lipoprotein metabolism*

14 Vitamin E in Health and Disease

*3.4.4. Other relevant pathophysiological factors*

vitamin E without affecting lipoprotein homeostasis.

vitamin E.

**4. Conclusion**

After its intestinal absorption, the transport of vitamin E, including its transfer to and its export from the liver as well as the subsequent distribution of vitamin E in the human body, strictly depends on different lipoproteins [7]. Thus, disorders of the lipoprotein metabolism can lead to disturbances of vitamin E homeostasis. Abetalipoproteinemia or Bassen-Kornzweig syndrome is a rare form of neurodegenerative ataxia with a strong impact on the hepatic handling of vitamin E. Abetalipoproteinemia is caused by mutations in the gene encoding for the microsomal triglyceride transfer protein (MTP), which is required for the assembly and secretion of the apolipoprotein B (apoB) forms in the liver and the intestine [154]. The apoB forms are the primary apolipoproteins associated to chylomicrons or VLDL, IDL, and LDL, respectively, and are thus essential for the distribution of vitamin E in the human body [7, 155]. As a result of the disturbed intestinal absorption and hepatic excretion of all lipid soluble molecules, patients with abetalipoproteinemia show vitamin E deficiency as well as low serum concentrations of cholesterol and triglycerides [156]. Next, the hepatic handling of vitamin E can be affected by familial hypobetalipoproteinemia. This lipoprotein disorder is caused by mutations in the *APOB* gene, leading to disturbances of translation of the apoB proteins and/or impaired secretion of VLDL [157]. Thus, familial hypobetalipoproteinemia displays the same clinical features as abetalipoproteinemia. In summary, lipoprotein disorders exert clear impact on the hepatic and systemic handling of

AVED is a neurological disorder, which has for the first time been described in a 12-year-old boy with cerebellar ataxia and low serum vitamin E concentrations. Interestingly, the boy showed no lipid malabsorption or a lack of lipoproteins, like it has been observed in abetalipoproteinemia [158]. Subsequent studies identified a mutation in the *TTPA* gene, the gene encoding for α-TTP, as the disease causing factor [159]. Thus, AVED patients have impaired expression of α-TTP, leading to impaired incorporation of vitamin E (α-TOH) into VLDL as well as a higher metabolic conversion and excretion of vitamin E [154]. In addition, AVED patients show very low plasma vitamin E concentrations together with normal absorption rates for vitamin E in the absence of intestinal malabsorption and abetalipoproteinemia [2, 154]. In summary, AVED represents a clinical condition that includes altered hepatic handling of

In the last decades of vitamin E research, the liver appeared as the central organ for the uptake, distribution, metabolism, and storage of vitamin E. Thus, it is also a starting point for various strategies for the modulation of the vitamin E homeostasis. Based on current knowledge, we identified physiological, nonphysiological as well as pathophysiological factors influencing the hepatic handling of vitamin E, verifying the crucial role of the liver in vitamin E homeostasis (a brief schematic overview is provided in **Figure 1**). Nevertheless, further studies The work of S.L. is supported by grants from the Federal Ministry of Education and Research (01EA1411A), the Deutsche Forschungsgemeinschaft (DFG; RTG 1715), and the German Ministry of Economics and Technology (AiF 16642 BR) via AiF (German Federation of Industrial Research Associations) and FEI (Research Association of the German Food Industry) and by the Free State of Thuringia and the European Social Fund (2016 FGR 0045). The work of L.S. is supported by the Free State of Thuringia and the European Social Fund (2016 FGR 0045). The work of M.W. is also funded by the DFG (Wa 3836/1-1).
