Vitamin E sequestration by liver fat in humans.

BACKGROUNDWe hypothesized that obesity-associated hepatosteatosis is a pathophysiological chemical depot for fat-soluble vitamins and altered normal physiology. Using α-tocopherol (vitamin E) as a model vitamin, pharmacokinetics and kinetics principles were used to determine whether excess liver fat sequestered α-tocopherol in women with obesity-associated hepatosteatosis versus healthy controls.METHODSCustom-synthesized deuterated α-tocopherols (d3- and d6-α-tocopherols) were administered to hospitalized healthy women and women with hepatosteatosis under investigational new drug guidelines.

Vitamin E: Mechanism of transport and regulation in the CNS.

Although vitamin E has been recognized as a critical micronutrient to neuronal health for more than half a century, vitamin E transport and regulation in the brain remain a mystery. Currently, the majority of what is known about vitamin E transport has been delineated in the liver. However, clues from the pathogenesis of neurological-related vitamin E deficient diseases point to compromised neuronal integrity and function, underlining the critical need to understand vitamin E regulation in the CNS.

Vitamin E and Alzheimer's Disease-Is It Time for Personalized Medicine?

For the last two decades, it has been hotly debated whether vitamin E-the major lipid-soluble antioxidant, which functions to maintain neurological integrity-is efficacious as a therapy for Alzheimer's disease. Several factors key to the debate, include (1) which of the eight naturally-occurring vitamin E forms should be used; (2) how combination treatments affect vitamin E efficacy; and (3) safety concerns that most-recently resurfaced after the results of the Selenium and vitamin E Cancer prevention trial SELECT prostate cancer trial. However, with the advent of new genetic technologies and identifications of vitamin E-modulating single nucleotide polymorphisms (SNPs), we propose that clinical trials addressing the question "Is vitamin E an effective treatment for Alzheimer's disease" should consider a more focused and personalized medicine approach to designing experiments.

Synthesis and characterization of a fluorescent probe for α-tocopherol suitable for fluorescence microscopy.

Previously prepared fluorescent derivatives of α-tocopherol have shown tremendous utility in both in vitro exploration of the mechanism of ligand transfer by the α-tocopherol transfer protein (α-TTP) and the intracellular transport of α-tocopherol in cells and tissues. We report here the synthesis of a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) containing α-tocopherol analog having extended conjugation with an alkenyl thiophene group that extends the absorption and emission maxima to longer wavelengths (λex=571nm and λem=583nm). The final fluorophore thienyl-ene-BODIPY-α-tocopherol, 2, binds to recombinant human α-TTP with a Kd=8.

Vitamin E and neurodegeneration.

Alpha-tocopherol (vitamin E) is a plant-derived antioxidant that is essential for human health. Studies with humans and with animal models of vitamin E deficiency established the critical roles of the vitamin in protecting the central nervous system, and especially the cerebellum, from oxidative damage and motor coordination deficits. We review here the established roles of vitamin E in protecting cerebellar functions, as well as emerging data demonstrating the critical roles of alpha-tocopherol in preserving learning, memory and emotive responses.

Vitamin E trafficking in neurologic health and disease.

Vitamin E was identified almost a century ago as a botanical compound necessary for rodent reproduction. Decades of research since then established that of all members of the vitamin E family, α-tocopherol is selectively enriched in human tissues, and it is essential for human health. The major function of α-tocopherol is thought to be that of a lipid-soluble antioxidant that prevents oxidative damage to biological components.

Expression of the α-tocopherol transfer protein gene is regulated by oxidative stress and common single-nucleotide polymorphisms.

Vitamin E (α-tocopherol) is the major lipid-soluble antioxidant in most animal species. By controlling the secretion of vitamin E from the liver, the α-tocopherol transfer protein regulates whole-body distribution and levels of this vital nutrient. However, the mechanism(s) that regulates the expression of this protein is poorly understood.

The α-tocopherol transfer protein is essential for vertebrate embryogenesis.

The hepatic α-tocopherol transfer protein (TTP) is required for optimal α-tocopherol bioavailability in humans; mutations in the human TTPA gene result in the heritable disorder ataxia with vitamin E deficiency (AVED, OMIM #277460). TTP is also expressed in mammalian uterine and placental cells and in the human embryonic yolk-sac, underscoring TTP's significance during fetal development. TTP and vitamin E are essential for productive pregnancy in rodents, but their precise physiological role in embryogenesis is unknown.

Strain-specific variants of the mouse Cftr promoter region reveal transcriptional regulatory elements.

Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels is not well understood. Mouse Cftr mRNA shows strain-dependent expression differences that cannot be fully explained by variation at non-Cftr loci. Differences in tracheal and colonic expression appear to be due predominantly to elements linked to Cftr.