Abstract: The present disclosure provides FGF1 mutant proteins, which include an N-terminal deletion, point mutation(s), or combinations thereof, as well as FGF1-vagus targeting chimeric proteins which include an FGF1 portion (e.g., native FGF1 or mutant FGF1) and a portion that targets the chimera to the vagus nerve (e.g., GLP or exendin-4). Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. The disclosed FGF1 mutants and FGF1-vagus targeting chimeric proteins can reduce blood glucose in a mammal, and in some examples are used to treat a metabolic disorder.

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: Novel compounds having a formula 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: 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: Novel compounds having a formula 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: 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: The invention features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.

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: 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 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 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 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: The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency. In particular embodiments the invention is predicated upon increased expression of an estrogen related receptor and changes in the oxidative and glycolytic pathways.

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.

Abstract: Disclosed are embodiments of a method of treating or preventing latent autoimmune diabetes of adults (LADA) in a subject. Such embodiments include administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or farnesoid X receptor (FXR) agonist compounds, thereby activating FXR receptors in the intestines, and treating or preventing latent autoimmune diabetes of adults (LADA) in the subject.

Abstract: The present disclosure provides FGF1 mutant proteins having one or more mutations in the heparin binding domain. Such mutants may also have 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: The present disclosure provides FGF1 mutant proteins having one or more mutations in the heparin binding domain. Such mutants may also have 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: 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: This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERR? activity to the subject. Such agents can include one or more ERR? agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).

Abstract: The invention features compositions comprising in vitro generated beta cells capable of glucose-stimulated insulin secretion, methods of inducing beta cell maturation from embryonic or induced pluripotent stem cell-derived beta-like cells, and methods of using in vitro generated beta cells for the treatment of type 1 diabetes, type 2 diabetes, or a related disorder.