Abstract: The present invention provides for a novel lipokine, trans-C16:ln 7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, low concentrations of trans-C16:ln 7-palmitoleate the serum indicates a risk of metabolic disease. Additionally, administering trans C16:ln 7-palmitoleate to a subject (via pharmaceutical, nutraceutical, or other means), positively impacts glucose metabolism.

Abstract: The present invention provides for a novel lipokine, trans-C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, low concentrations of trans-C16:1n7-palmitoleate the serum indicates a risk of metabolic disease. Additionally, administering trans C16:1n7-palmitoleate to a subject (via pharmaceutical, nutraceutical, or other means), positively impacts glucose metabolism.

Abstract: The embodiments of the invention provide for genetic, chemical or dietary interventions that modulate hepatic phospholipid synthesis and/or endoplasmic reticulum (ER) calcium homeostasis function. More specifically, the present invention addresses modulation of the lipid composition of the hepatic stressed ER and/or improvement of the hepatic ER calcium metabolism to reduce ER stress and thus treat type 2 diabetes, fatty liver disease, atherosclerosis, inflammation, and/or dislipidemia.

Abstract: Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

Abstract: The present invention provides for a novel lipokine, trans-C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, low concentrations of trans-C16:1n7-palmitoleate the serum indicates a risk of metabolic disease. Additionally, administering trans C16:1n7-palmitoleate to a subject (via pharmaceutical, nutraceutical, or other means), positively impacts glucose metabolism.

Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.

Abstract: The present invention provides for a novel lipokine, C16:1n7-palmitoleate, which also serves as a biomarker for metabolic status. More specifically, a low concentration of C16:1n7-palmitoleate in the free acid component of the serum indicates a risk of metabolic disease, and that de novo lipogenesis should be stimulated. Additionally, administering C16:1n7-palmitoleate to a subject (via nutraceutical or other means), positively impacts lipid metabolism.

Abstract: Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheral insulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating obesity-associated diseases.

Abstract: Endoplasmic reticulum stress has been found to be associated with the genetic disease tuberous sclerosis. Tuberous sclerosis is cause by defects in the two genes, TSC1 and TSC2. Agents that modulate ER stress may be used to treat tuberous sclerosis and other hamartomatous diseases. In particular, 4-phenyl butyric acid (PBA) has been shown to reduce ER stress is TSC-deficient cells. Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide arid glycerol may also be useful in treating tuberous sclerosis. The present invention provides methods of treating a subject suffering from tuberous sclerosis using ER stress reducers such as PBA, TUDCA, UDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in TSC-deficient cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating tuberous sclerosis.

Abstract: The invention provides compounds and pharmaceutical compositions that can be used to treat or prevent atherosclerosis, stroke, and other ischemic vascular diseases, dyslipidemia and hypercholestcrolemia and prevent complications of these conditions. Agents in accordance with the invention include; tauroursodeoxycholic acid (TUDCA), and analogs and derivatives thereof; 4-phenyl butyric acid (PBA), and analogs and derivatives thereof; and trimethyl N-oxide (TMAO), and analogs and derivatives thereof.

Abstract: The invention features a method of inhibiting formation of atherosclerotic lesions by administering to a mammal, e.g., a human patient who has been identified as suffering from or at risk of developing atherosclerosis, a compound that reduces expression or activity of AFABP.

Abstract: Disclosed herein are compositions and methods used to modulate a NH2-terminal Jun Kinase activity. These compositions and methods can be employed to regulate metabolic disorders associated with, for example, insulin such as diabetes. The reduction in NH2-terminal Jun Kinase activity can lead to the reduction in weight and improve insulin sensitivity.

Abstract: The invention provides compositions and methods of inhibiting Mal1 expression or function to treat lipid metabolisms disorders.

Abstract: The invention features compositions and methods for inhibiting adipogenesis by increasing GATA-2 or GATA-3 expression. Also included are methods of treating lipdystrophy by decreasing GATA-2 or GATA-3 expression.

Abstract: The invention provides compositions and methods of inhibiting Mal1 expression or function to treat lipid metabolisms disorders.

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.