Hui Tian

Bio: Hui Tian is an academic researcher from University of Texas System. The author has contributed to research in topics: Sitosterolemia & Blood lipids. The author has an hindex of 2, co-authored 5 publications receiving 1523 citations. Previous affiliations of Hui Tian include University of Texas Southwestern Medical Center.

Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters

Abstract: In healthy individuals, acute changes in cholesterol intake produce modest changes in plasma cholesterol levels. A striking exception occurs in sitosterolemia, an autosomal recessive disorder characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia, and premature coronary atherosclerosis. We identified seven different mutations in two adjacent, oppositely oriented genes that encode new members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family (six mutations in ABCG8 and one in ABCG5) in nine patients with sitosterolemia. The two genes are expressed at highest levels in liver and intestine and, in mice, cholesterol feeding up-regulates expressions of both genes. These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis.

ABCG8 vectors, host cells, and method of making

Abstract: The present invention provides nucleic acids encoding a novel ABC family cholesterol transporter, ABCG8. The herein-disclosed sequences can be used for any of a number of purposes, including for the diagnosis and treatment of cholesterol-associated disorders, including sitosterolemia, and for the identification of molecules that associate with and/or modulate the activity of ABCG8.

ABCG5 and ABCG8: compositions and methods of use

Abstract: The present invention provides nucleic acids encoding a novel ABC family cholesterol transporter, ABCG8. The herein-disclosed sequences can be used for any of a number of purposes, including for the diagnosis and treatment of cholesterol-associated disorders, including sitosterolemia, and for the identification of molecules that associate with and/or modulate the activity of ABCG8.

Abcg5 et abcg8: compositions et procedes d'utilisation

Abstract: Cette invention se rapporte a des acides nucleiques codant un nouveau transporteur de cholesterol de la famille ABC, le transporteur ABCG8. Les sequences decrites ici peuvent etre utilisees dans une grande variete d'applications, notamment le diagnostic et le traitement des troubles associes au cholesterol, tels que la sitosterolemie, ainsi que l'identification de molecules qui s'associent au transporteur ABCG8 et/ou qui en modulent l'activite.

Gene de susceptibilite a la sitosterolemie (ssg): compositions et methodes d'utilisation

Abstract: L'invention concerne des acides nucleiques codant un nouveau transporteur de cholesterol de la famille ABC, le SSG. Selon l'invention, les sequences peuvent etre utilisees a des fins tres variees, y compris pour le diagnostic et le traitement de troubles lies au cholesterol, comprenant la sitosterolemie, ainsi que pour l'identification de molecules associees a l'activite de SSG et/ou la modulant.

Nuclear receptors and lipid physiology: opening the X-files.

Abstract: Cholesterol, fatty acids, fat-soluble vitamins, and other lipids present in our diets are not only nutritionally important but serve as precursors for ligands that bind to receptors in the nucleus. To become biologically active, these lipids must first be absorbed by the intestine and transformed by metabolic enzymes before they are delivered to their sites of action in the body. Ultimately, the lipids must be eliminated to maintain a normal physiological state. The need to coordinate this entire lipid-based metabolic signaling cascade raises important questions regarding the mechanisms that govern these pathways. Specifically, what is the nature of communication between these bioactive lipids and their receptors, binding proteins, transporters, and metabolizing enzymes that links them physiologically and speaks to a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.

The Human ATP-Binding Cassette (ABC) Transporter Superfamily

Abstract: The ATP-binding cassette (ABC) transporter superfamily contains membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes. Genetic variation in these genes is the cause of or contributor to a wide variety of human disorders with Mendelian and complex inheritance, including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response. Conservation of the ATP-binding domains of these genes has allowed the identification of new members of the superfamily based on nucleotide and protein sequence homology. Phylogenetic analysis is used to divide all 48 known ABC transporters into seven distinct subfamilies of proteins. For each gene, the precise map location on human chromosomes, expression data, and localization within the superfamily has been determined. These data allow predictions to be made as to potential functions or disease phenotypes associated with each protein. In this paper, we review the current state of knowledge on all human ABC genes in inherited disease and drug resistance. In addition, the availability of the complete Drosophila genome sequence allows the comparison of the known human ABC genes with those in the fly genome. The combined data enable an evolutionary analysis of the superfamily. Complete characterization of all ABC from the human genome and from model organisms will lead to important insights into the physiology and the molecular basis of many human disorders.

Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.

Abstract: Dietary cholesterol consumption and intestinal cholesterol absorption contribute to plasma cholesterol levels, a risk factor for coronary heart disease. The molecular mechanism of sterol uptake from the lumen of the small intestine is poorly defined. We show that Niemann-Pick C1Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol. NPC1L1 expression is enriched in the small intestine and is in the brush border membrane of enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice exhibit a substantial reduction in absorbed cholesterol, which is unaffected by dietary supplementation of bile acids. Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.

Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs

Abstract: Highly potent, but poorly water-soluble, drug candidates are common outcomes of contemporary drug discovery programmes and present a number of challenges to drug development - most notably, the issue of reduced systemic exposure after oral administration. However, it is increasingly apparent that formulations containing natural and/or synthetic lipids present a viable means for enhancing the oral bioavailability of some poorly water-soluble, highly lipophilic drugs. This Review details the mechanisms by which lipids and lipidic excipients affect the oral absorption of lipophilic drugs and provides a perspective on the possible future applications of lipid-based delivery systems. Particular emphasis has been placed on the capacity of lipids to enhance drug solubilization in the intestinal milieu, recruit intestinal lymphatic drug transport (and thereby reduce first-pass drug metabolism) and alter enterocyte-based drug transport and disposition.