Abstract: The present disclosure provides FGF2 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Thus, the disclosed mutant FGF2 proteins can be used to treat one or more metabolic diseases. In some examples, mutant FGF2 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels, for example to treat a metabolic disorder are also provided.

Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

Abstract: Novel FXR agonists are disclosed, embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Abstract: Methods of using FGF1 analogs, such as FGF1 mutant proteins having an N-terminal deletion, point mutation(s), or combinations thereof, to reduce blood glucose levels in subjects with steroid-induced diabetes, hypercortisolemia, or diabetes due to treatment with an antipsychotic agent, are provided. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1-binding protein, a ?-Klotho-binding protein and a FGFR1-binding protein, a C-terminal region from FGF19 or FGF21.

Abstract: Provided herein are deuterated compounds and compositions useful in increasing PPAR? activity. The compounds have a formula where L5 comprises at least one deuterium. Exemplary species include The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

Abstract: Brown adipose tissue (BAT) plays a role in keeping an organism warm in response to a cold environment. In response to cold, transcription factors, including peroxisome proliferator receptor alpha (PGC1?), mediate the adaptive changes in the expression of oxidative and thermogenic genes in BAT. However, even without cold, BAT exhibits high expression of these genes relative to white adipose tissue (WAT). It is shown herein that estrogen related receptor gamma (ERR?) is a critical factor that controls the expression of key metabolic genes in BAT under basal conditions. ERR? is highly expressed in BAT versus WAT, yet is not transcriptionally induced by cold, suggesting it plays an important role in innate basal BAT function rather than in the adaptive response to cold. Based on these observations, methods of increasing thermogenesis in a subject by administering a therapeutically effective amount of one or more agents that increase ERR? activity are provided.

Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.

Abstract: Provided herein are methods of treating pancreatic ductal adenocarcinoma in a mammalian subject. In some examples, such methods include administering a therapeutically effective amount of a VDR agonist (such as calcipotriol and/or paricalcitol) and administering a therapeutically effective amount of one or more chemotherapeutic agents, wherein the one or more chemotherapeutic agents comprise gemcitabine, 5-fluorouracil, cisplatin, protein-bound paclitaxel, and a PD-1 monoclonal antibody and/or PDL-1 monoclonal antibody.

Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: Provided herein are compounds and compositions useful in increasing PPAR? activity. The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

Abstract: Provided herein are compounds and compositions useful in increasing PPAR? activity. The compounds and compositions provided herein are useful for the treatment of PPAR? related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: The present disclosure provides chimeric proteins having an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor (FGF) 2 and the C-terminus comprises a portion of an FGF1 protein, wherein the chimeric protein comprises at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12 or 13. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that increases the biological activity of the vitamin D receptor (VDR) (e.g., a VDR agonist), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell. Such methods can be used to treat or prevent fibrosis.

Abstract: The present disclosure provides FGF1 mutant proteins, which include an N-terminal deletion, point mutation(s), or combinations thereof. In some examples, the mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. The disclosed FGF1 mutants can reduce blood glucose in a mammal, and in some examples are used to treat a metabolic disorder.

Abstract: Provided herein are methods and compositions for treating lipodystrophy using fibroblast growth factor 1 (FGF-1) compounds.

Abstract: Provided herein are methods of treating and preventing pancreatitis, such as pancreatitis induced by glucagon-like peptide (GLP) agonists (such as GLP-1 agonists, for example Byetta®), by administration of a vitamin D receptor agonist (such as vitamin D, vitamin D analogs, vitamin D precursors, and vitamin D receptor agonists precursors). In some examples the subject has diabetes, such as type 2 diabetes.

Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.

Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that increases the biological activity of the vitamin D receptor (VDR) (e.g., a VDR agonist), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell. Such methods can be used to treat or prevent fibrosis.

Abstract: Provided herein are methods and kits for increasing cardiac contraction, increasing mitochondrial activity, and/or increasing oxphos activity. Such methods include use of therapeutically effective amounts of one or more agents that increases estrogen-related receptor (ERR) ? activity and one or more agents that increases ERR? activity. In some examples, the method further includes administering a therapeutically effective amount of one or more agents that increases mitofusin 1 (Mfn1) activity.