Abstract: The invention provides isolated nucleic acid molecules, designated PGC-1&bgr; 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&bgr; nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1&bgr; gene has been introduced or disrupted. The invention still further provides isolated PGC-1&bgr; proteins, fusion proteins, antigenic peptides and anti-PGC-1&bgr; 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 PPAR&ggr; is expressed consistently in each of the major histologic types of human liposarcoma. It has further been discovered that maximal activation of PPAR&ggr; with exogenous ligand (a thiazolidinedione or derivative thereof) promotes terminal differentiation of primary human liposarcoma cells. It has still further been discovered that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR&ggr;/RXR&agr; heterodimer, and that simultaneous treatment of liposarcoma cells with a thiazolidinedionyl moiety (a PPAR&ggr;-selective class of compounds) and an RXR-specific ligand results in an additive stimulation of differentiation. Accordingly, according to the invention, there have been identified compositions which are useful for the treatment of liposarcomas.

Abstract: Novel FDRG polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length FDRG proteins, the invention further provides isolated FDRG fusion proteins, antigenic peptides and anti-FDRG antibodies. The invention also provides FDRG nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a FDRG gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

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.

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 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 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.

Abstract: A method for inhibiting proliferation of a PPAR &ggr;-responsive hyperproliferative cell which comprises the step of contacting the cell with (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is disclosed. A method for treating or prophylactically preventing in an animal subject a disorder characterized by unwanted proliferation of PPAR&ggr;-responsive hyperproliferative cells which comprises administering to the subject (I) an inhibitory amount of a PPAR&ggr; agonist and (II) a MAP kinase inhibitor is also disclosed. Pharmaceutical compositions comprising a therapeutically effective amount of a PPAR&ggr; agonist and a MAP kinase inhibitor are disclosed for use in the methods.

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: An induction of TNF-.alpha. mRNA expression has been observed in adipose tissue from four different insulin resistant rodent models of obesity and diabetes. TNF-.alpha. protein was also elevated locally and systemically. Neutralization of TNF-.alpha. in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. A method of treating an animal suffering from insulin resistance in obesity linked Type II diabetes mellitus is disclosed. The method includes providing a therapeutic agent that includes an antagonist to TNF-.alpha. function in a pharmaceutically acceptable carrier substance and administering a pharmacologically effective amount of the therapeutic agent to the animal.

Abstract: An induction of TNF-.alpha. mRNA expression has been observed in adipose tissue from four different insulin resistant rodent models of obesity and diabetes. TNF-.alpha. protein was also elevated locally and systemically. Neutralization of TNF-.alpha. in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. A method of treating an animal suffering from insulin resistance in obesity linked Type II diabetes mellitus is disclosed. The method includes providing a therapeutic agent that includes an antagonist to TNF-.alpha. function in a pharmaceutically acceptable carrier substance and administering a pharmacologically effective amount of the therapeutic agent to the animal.

Abstract: Regulatory DNA sequences are provided, which are obtained from the 5' flanking region of genes which are expressed primarily in differentiated adipose tissue. These DNA sequences are largely responsible for driving the expression of endogenous genes specifically in adipose tissue in vivo. The DNA sequences can be located in a region 5' of the gene, distinct from promoter sequences which provide a site for the initiation of transcription into DNA, or can be located within the region of the promoter itself.When operatively linked to a gene encoding a recombinant protein capable of exerting an effect on the metabolism of adipocytes, the DNA sequences of the invention can be used to produce transgenic animals which exhibit altered fat tissue metabolism. Depending upon the nature of the gene introduced in the animal or ancestor thereof at an embryonic stage, the transgenic animals are leaner or more obese than non-transgenic animals of the same species.

Abstract: The invention provides a novel method of effecting vasodilation in a warm-blooded animal in need of such treatment and involves administering to a warm-blooded animal an effective amount of a vasodilatory monoglyceride of the formula: ##STR1## wherein R is a straight or branched chain aliphatic hydrocarbyl substituent of 2-7 carbon atoms, preferably 3-5 carbon atoms, which is saturated or unsaturated, and which is substituted or unsubstituted with one or more substituents that do not interfere with vasodilatory activity.

Abstract: The invention provides a recombinant purified human protein in substantial quantities which has both adipsin and complement D activity. The invention also provides materials and methods to produce the protein. In addition, antibodies immunoreactive with this protein are useful to diagnose metabolic defects attributable to adipsin deficiency or complement D deficiency. The protein can be used to treat obesity caused by adipsin deficiency or to treat subjects for infection.

Abstract: Monoglycerides of the formula: ##STR1## wherein R is an aliphatic hydrocarbyl moiety of 2-10 C, straight chain or branched, saturated or unsaturated, and optionally substituted with one or more substituents which do not interfere with angiogenic activity are capable of stimulating angiogenesis in vivo. These compounds, and their pharmaceutical compositions, are useful in wound healing and other therapeutic applications where stimulation of vascularization is beneficial. Antibodies to these materials have also been prepared and are useful in diagnosis and therapy.