University of California

The J. David Gladstone Institutes

The United States Government As Represented by the Department of Veterans Affairs

Other

Robert V Farese, Jr

Sylvaine Cases

Sandra K Erickson

Steven J Smith

Thomas L Innerarity

Ping Zhou

Sabine Novak

Michel Accad

Scot J Stone

Erwin H Ludwig

Peter Walter

Karl H Weisgraber

Robert L Raffai

Tobias C Walther

Hubert C Chen

Li-Ming Dong

Yi Guo

Chi-Liang Eric Yen

The present invention is based on the discovery of a set of genes that are involved in lipid-droplet formation and regulation. Accordingly, the present invention provides methods of increasing or decreasing lipid concentrations in eukaryotic cells by decreasing or increasing expression of one of these genes. Increased lipid concentrations may be useful, for example, in the generation of biofuels. Decreased lipid concentration may be useful in the treatment of diseases characterized by excessive lipid storage. In addition, the invention provides methods of identifying markers of diseases characterized by excessive lipid storage.

Methods of modulating lipid concentrations in eukaryotic cells

Nucleic acid compositions encoding mammalian DGAT2&#x3b1; polypeptide products with diglyceride acyltransferase activity, as well as the mammalian DGAT2&#x3b1; polypeptide products encoded thereby and methods for producing the same, are provided. The subject DGAT2&#x3b1; polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.

Diacylglycerol O-acyltransferase 2&#x3b1; (DGAT2&#x3b1;)

Methods and compositions for modulating carbohydrate metabolism in a host are provided. In the subject methods, diacylglycerol acyltransferase (DGAT) activity (specifically DGAT1 activity) is modulated, e.g., reduced or enhanced, to achieve a desired insulin and/or leptin sensitivity, thereby modulating carbohydrate metabolism, e.g., increasing or decreasing blood glucose levels, glucose uptake into cells and assimilation into glycogen. Also provided are pharmaceutical compositions for practicing the subject methods. The subject methods and compositions find use in a variety of applications, including the treatment of hosts suffering conditions associated with abnormal carbohydrate metabolism, such as obesity or diabetes.

Genetically modified mouse lacking diacylglycerol acyltransferase-1 (DGAT-1) activity

Nucleic acid compositions encoding novel ACAT proteins, as well as the novel ACAT-2 proteins, (ACAT-2) are provided. Also provided are methods of producing the subject nucleic acid and protein compositions. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including diagnostic and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with ACAT-2 activity, e.g., in the treatment of gall stones.

Acyl CoA:cholesterol acyltransferase (ACAT-2)

The invention provides gene-targeted non-human animals comprising a genetically modified apoE gene encodes a recombinant apoE polypeptide displaying domain interaction. The invention further provides cells isolated from the gene-targeted animals, which cells produce a recombinant apoE polypeptide displaying domain interaction. The invention further provides methods of identifying agents that reduce apoE4 domain interaction, and which are useful to treat apoE4-related neurological and cardiovascular disorders.

Gene-targeted animal model of apolipoprotein E4 domain interaction and uses thereof

Nucleic acid compositions encoding polypeptide products with diglyceride acyltransferase and/or monoacylglycerol acyltransferase activity, as well as the polypeptide products encoded thereby, i.e., mammalian DGAT2&#x3b1; and MGAT1 polypeptide products, and methods for producing the same, are provided. Also provided are: methods and compositions for modulating DGAT2&#x3b1; and MGAT1 activity; DGAT2&#x3b1; and MGAT1 transgenic cells, animals and plants, as well as methods for their preparation; and methods for making diglyceride, diglyceride compositions, triglycerides and triglyceride compositions, as well as the compositions produced by these methods. The subject methods and compositions find use in a variety of different applications, including research, medicine, agriculture and industry applications.

Mono- and diacylglycerol acyltransferases and methods of use thereof

The present invention provides isolated an polynucleotide comprising a polymorphic nucleotide sequence from a diacylglycerol acyltransferase (DGAT) gene, wherein at least one a polymorphism is associated with a condition relating to DGAT activity. The invention further provides diagnostic assays for detecting the presence in a nucleic acid sample of a polymorphism in a DGAT gene that is associated with a condition relating to DGAT activity, and for detecting a propensity to develop a condition associated with DGAT activity. The invention further provides treatment methods.

Polymorphisms in a diacylglycerol acyltransferase gene, and methods of use thereof

Nucleic acid compositions encoding novel ACAT proteins, as well as the novel ACAT-2 proteins, (ACAT-2) are provided. Also provided are methods of producing the subject nucleic acid and protein compositions. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies for disease conditions associated with ACAT-2 activity.

Nucleic acid compositions encoding polypeptide products with diglyceride acyltransferase activity, as well as the polypeptide products encoded thereby and methods for producing the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.

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San Francisco, CA, United States of America

Robert V Farese, Jr