Abstract: The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject. The present invention also relates to the use of PGC-1 expression levels to determine the safe dosage range for known or putative respiration uncoupling agents for use as anti-obesity therapeutics. The present invention further relates to methods for identifying new compounds that have respiration uncoupling activity.

Abstract: The present invention is based on the finding that activation of PPAR? plays a key role in inducing growth arrest and differentiation of certain actively proliferating cells. We show that administration of PPAR? agonists, such as thiazolidinedione ligands (TZDs), is effective both in vitro and in vivo at inhibiting the proliferation of such cells.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1b and PGC-1c nucleic acid molecules, which encode novel isoforms of PGC-1 family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: The present invention provides methods for modulating mitochondrial function, modulating lesion formation in the brain, modulating neurite growth, modulating neuronal degeneration, and treating and preventing neurological diseases or disorders comprising modulating the expression or activity of PGC-1?. The present invention also provides an animal, e.g., transgenic mouse, in which the PGC-1? gene is misexpressed. Methods for identifying compounds which are capable of treating or preventing a neurological disease or disorder are also described.

Abstract: The present invention relates to therapeutic compositions for treating or preventing obesity and obesity-related disorders in a subject. The present invention also relates to the use of PGC-1 expression levels to determine the safe dosage range for known or putative respiration uncoupling agents for use as anti-obesity therapeutics. The present invention further relates to methods for identifying new compounds that have respiration uncoupling activity.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1? nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1? nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1? gene has been introduced or disrupted. The invention still further provides isolated PGC-1? proteins, fusion proteins, antigenic peptides and anti-PGC-1? antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides novel methods and compositions for modulating gluconeogenesis through modulation of PGC-1 activity or expression. Also provided are methods for identifying compounds that modulate gluconeogenesis through modulation of PGC-1 activity or expression, as well as methods for identifying compounds that modulate the interaction of PGC-1 with PGC-1 target molecules. Further provided are methods for treating disorders characterized by aberrant gluconeogenesis.

Abstract: The present invention provides methods for treating lipid-related diseases and disorders, e.g., hyperlipidemia, hyper-triglyceridemia, hypercholesterolemia, cardiovascular disease, obesity, and type II diabetes, and for modulating lipid biosynthesis, lipid transport, plasma triglyceride levels and/or plasma cholesterol levels, by modulating the expression or activity of PGC-1?. Methods for identifying compounds which are capable of treating or preventing a lipid-related disease or disorder are also described.

Abstract: The invention provides novel methods and compositions for modulating gluconeogenesis through modulation of PGC-1 activity or expression. Also provided are methods for identifying compounds that modulate gluconeogenesis through modulation of PGC-1 activity or expression, as well as methods for identifying compounds that modulate the interaction of PGC-1 with PGC-1 target molecules. Further provided are methods for treating disorders characterized by aberrant gluconeogenesis.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1? nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1? nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1? gene has been introduced or disrupted. The invention still further provides isolated PGC-1? proteins, fusion proteins, antigenic peptides and anti-PGC-1? antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1b and PGC-1c nucleic acid molecules, which encode novel isoforms of PGC-1 family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1? nucleic acid molecules, which encode novel PGC-1 related coactivator molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1? nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1? gene has been introduced or disrupted. The invention still further provides isolated PGC-1? proteins, fusion proteins, antigenic peptides and anti-PGC-1? antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: In accordance with the present invention, it has been discovered that CREB regulates hepatic gluconeogenesis via the co-activator, PGC-1. PGC-1 potentiated glucocorticoid induction of the gene for PEPCK, the rate limiting enzyme in gluconeogenesis, via the glucocorticoid response unit in the promoter, indicating that activation of PGC-1 by CREB in liver contributes to the pathogenesis of diabetes mellitus. In accordance with the above discoveries, the present invention provides a method of identifying a compound that modulates gluconeogenesis. The invention method comprises contacting CREB and a nucleic acid comprising a PGC-1 promoter with a test compound, and determining if the test compound modulates binding between CREB and the PGC-1 promoter.

Abstract: The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1b and PGC-1c nucleic acid molecules, which encode novel isoforms of PGC-1 family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of body weight disorders, including, but not limited to, obesity, overweight, anorexia, cachexia, insulin resistance, and diabetes. The invention further provides methods for identifying a compound capable of treating a body weight disorder or modulating thermogenesis. The invention also provides a method for modulating thermogenesis, e.g., modulating thermogenesis in a subject. In addition, the invention provides a method for treating a subject having a body weight disorder characterized by aberrant DHDR-2 polypeptide activity or aberrant DHDR-2 nucleic acid expression. In another aspect, the invention provides methods for modulating thermogenesis in a subject.

Abstract: The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of body weight disorders, including, but not limited to, obesity, overweight, anorexia, cachexia, insulin resistance, and diabetes. The invention further provides methods for identifying a compound capable of treating a body weight disorder or modulating thermogenesis. The invention also provides a method for modulating thermogenesis, e.g., modulating thermogenesis in a subject. In addition, the invention provides a method for treating a subject having a body weight disorder characterized by aberrant DHDR-2 polypeptide activity or aberrant DHDR-2 nucleic acid expression. In another aspect, the invention provides methods for modulating thermogenesis in a subject.

Abstract: The present invention is based on the finding that activation of PPAR&ggr; plays a key role in inducing growth arrest and differentiation of certain actively proliferating cells. We show that administration of PPAR&ggr; agonists, such as thiazolidinedione ligands (TZDs), is effective both in vitro and in vivo at inhibiting the proiferation of such cells.