Thermogenic compositions and methods
Thermogenic molecules and methods of using these molecules for treating or preventing a condition in a subject selected from the group consisting of visceral fat accumulation (e.g., Crohn's disease associated with visceral fat accumulation), obesity, diabetes, pre-diabetes, hypothermia, and chronic inflammation are disclosed. Also disclosed is a method for promoting glucose uptake in peripheral tissues (e.g., adipocytes and muscles) of a subject, enhancing nerve innervation in a subject, activating PI3 kinase in cell, and inducing leptin secretion by an adipocyte. Also disclosed are inhibitors of thermogenic molecules and methods of using these inhibitors to decrease thermogenesis of adipocytes in a subject. Also disclosed are self-assembled, biocompatible nanostructure non-covalently associated with a therapeutic or diagnostic peptide or peptidomimetic.
1 . A pharmaceutical composition comprising a self-assembled, biocompatible nanostructure non-covalently associated with a thermogenesis-inducing molecule,
wherein the thermogenesis-inducing molecule comprises epiregulin, insulin-like growth factor-binding protein 4 (IGFBP4), a disintegrin and metalloproteinase with thrombospondin type 1 motif 9 (ADAMT S9), semaphorin 3E, or a combination thereof,
wherein the self-assembled, biocompatible nanostructure comprises compound I
wherein the compound I is optionally functionalized at one or more side chains and/or at the C-terminus with a methyl, ethyl, t-butyl, or benzyl ester, and
wherein the compound I optionally contains a hydrophobic moiety covalently attached to the C-terminus.
2 . A method for treating a condition in a subject selected from the group consisting of visceral fat accumulation, obesity, diabetes, pre-diabetes, hypothermia, and chronic inflammation, comprising administering to the subject an effective amount of the composition of claim 1 .
3 . The method of claim 2 , wherein the composition is administered by injection or infusion.
4 . A method for promoting glucose uptake in peripheral tissues of a subject, comprising administering to the subject an effective amount of the composition of claim 1 .
5 . The method of claim 4 , further comprising administering to the subject a therapeutically effective amount of an epidermal growth factor receptor (EGFR) inhibitor, an erythroblastic oncogene B (ErbB) receptor inhibitor, a Mitogen-activated protein kinases (MAPK) inhibitor, or a combination thereof.
6 . The method of claim 4 , wherein the subject is resistant to insulin.
7 . The method of claim 4 , wherein the subject has diminished insulin production.
8 . The method of claim 4 , wherein the subject is obese.
9 . A method for enhancing nerve innervation in a subject, comprising administering to the subject an effective amount of the composition of claim 1 .