Abstract: Exemplary methods, compositions and uses thereof can be provided for preventing, reducing and/or treating loss of muscle function. In particular, e.g., it is possible to administer to a subject a pharmaceutical composition comprising a therapeutically effective amount of an agent that enhances Interleukin-6 (IL) release during exercise, and optionally a pharmaceutically acceptable carrier or excipient.

Abstract: Exemplary methods, compositions and uses thereof can be provided for preventing, reducing and/or treating loss of muscle function. In particular, e.g., it is possible to administer to a subject a pharmaceutical composition comprising a therapeutically effective amount of an agent that enhances Interleukin-6 (IL) release during exercise, and optionally a pharmaceutically acceptable carrier or excipient.

Abstract: Methods and compositions for treating frailty in mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin, e.g., by administration of undercarboxylated/uncarboxylated osteocalcin. The methods comprise alleviating at least one of: muscle wasting or a lung disorder while also alleviating at least one of: a metabolic disorder, a male reproductive disorder, or a cognitive disorder.

Abstract: Methods and compositions for treating or preventing cognitive disorders in mammals, preferably humans, are provided. The methods generally involve activation of the GPR158 signaling pathway involving osteocalcin, e.g., by administratin of undercarboxylated/uncarboxylated osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, cognitive loss due to neurodegeneration associated with aging, anxiety, depression, memory loss, learning difficulties, and cognitive disorders associated with food deprivation during pregnancy.

Abstract: Methods and compositions for treating or preventing cognitive disorders in mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin, e.g., by administration of undercarboxylated/uncarboxylated osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, cognitive loss due to neurodegeneration associated with aging, anxiety, depression, memory loss, learning difficulties, and cognitive disorders associated with food deprivation during pregnancy.

Abstract: Methods and compositions for treating frailty in mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin, e.g., by administration of undercarboxylated/uncarboxylated osteocalcin. The methods comprise alleviating at least one of: muscle wasting or a lung disorder while also alleviating at least one of: a metabolic disorder, a male reproductive disorder, or a cognitive disorder.

Abstract: The present invention relates to methods and compositions for treating and diagnosing disorders related to energy metabolism and the OST-PTP signaling pathway involving gamma-carboxylase, osteocalcin and adiponectin. Such disorders include, but are not limited to, metabolic syndrome, glucose intolerance, diabetes types 1 and 2, atherosclerosis and obesity.

Abstract: The present invention is directed to cell-based and non-cell based methods of drug screening to identify agents, or assay agents, that reduce OST-PTP or gamma-carboxylase activity or expression, or increase the level of undercarboxylated osteocalcin or adiponectin activity or expression. Such agents find use in treating or preventing a disorder related to the OST-PTP signaling pathway. Such disorders include, metabolic syndrome, glucose intolerance, type 1 or type 2 diabetes, atherosclerosis, or obesity. Such agents may be used to treat disorders characterized by decreased insulin production, deceased insulin sensitivity, and decreased glucose tolerance or increased fat mass.

Abstract: Methods and compositions for treating or preventing cognitive disorders in mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin, e.g., by administration of undercarboxylated/uncarboxylated osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, cognitive loss due to neurodegeneration associated with aging, anxiety, depression, memory loss, learning difficulties, and cognitive disorders associated with food deprivation during pregnancy.

Abstract: The present invention provides methods and therapeutic agents for lowering serum or plasma serotonin levels in a patient in order to prevent or treat diabetes. In preferred embodiments, the patient is known to have, or to be at risk for, diabetes and the agents are TPH1 inhibitors.

Abstract: Methods and compositions for treating, preventing, or diagnosing disorders related to reproduction in male mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-1B signaling pathway involving gamma-carboxylase and osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, male infertility, low sperm count, impaired sperm motility, impaired sperm viability, low testosterone levels, reduced libido, erectile dysfunction, underdevelopment of testes, and excess apoptosis in testes.

Abstract: The present invention provides methods and therapeutic agents for lowering or increasing serum serotonin levels in a patient in order to increase or decrease bone mass, respectively. In preferred embodiments, the patient is known to have, or to be at risk for, a low bone mass disease such as osteoporosis and the agents are TPH1 inhibitors or serotonin receptor antagonists.

Abstract: The present invention provides methods and therapeutic agents for lowering serum or plasma serotonin levels in a patient in order to prevent or treat diabetes. In preferred embodiments, the patient is known to have, or to be at risk for, diabetes and the agents are TPH1 inhibitors.

Abstract: Methods and compositions for treating, preventing, or diagnosing disorders related to reproduction in male mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-IB signaling pathway involving gamma-carboxylase and osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, male infertility, low sperm count, impaired sperm motility, impaired sperm viability, low testosterone levels, reduced libido, erectile dysfunction, underdevelopment of testes, and excess apoptosis in testes.

Abstract: The present invention provides methods and therapeutic agents for lowering or increasing serum serotonin levels in a patient in order to increase or decrease bone mass, respectively. In preferred embodiments, the patient is known to have, or to be at risk for, a low bone mass disease such as osteoporosis and the agents are TPH1 inhibitors or serotonin receptor antagonists.

Abstract: The present invention relates to methods and compositions for treating and diagnosing disorders related to energy metabolism and the OST-PTP signaling pathway involving gamma-carboxylase, osteocalcin and adiponectin. Such disorders include, but are not limited to, metabolic syndrome, glucose intolerance, diabetes types 1 and 2, atherosclerosis and obesity.

Abstract: The present invention provides methods and therapeutic agents for lowering or increasing serum serotonin levels in a patient in order to increase or decrease bone mass, respectively. In preferred embodiments, the patient is known to have, or to be at risk for, a low bone mass disease such as osteoporosis and the agents are TPH1 inhibitors or serotonin receptor antagonists.

Abstract: The present invention provides methods and therapeutic agents for lowering serum or plasma serotonin levels in a patient in order to prevent or treat hyperlipidemia or atherosclerosis. In preferred embodiments, the patient is known to have, or to be at risk for, hyperlipidemia or atherosclerosis and the agents are TPH1 inhibitors.

Abstract: Methods and compositions for treating, preventing, or diagnosing disorders related to reproduction in male mammals, preferably humans, are provided. The methods generally involve modulation of the OST-PTP signaling pathway or the PTP-IB signaling pathway involving gamma-carboxylase and osteocalcin. Disorders amenable to treatment by the methods include, but are not limited to, male infertility, low sperm count, impaired sperm motility, impaired sperm viability, low testosterone levels, reduced libido, erectile dysfunction, underdevelopment of testes, and excess apoptosis in testes.

Abstract: Methods for treating eating disorders associated with excessive weight gain, suppressing appetite, reducing body weight, or treating obesity in an animal by administering one or more antagonists of the serotonin Htr1a or Htr2b receptor, or a Tph2 inhibitor are provided, or combinations thereof.