34 results about "Brown adipose cell" patented technology

In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Nodal, anti-activin, and anti-GDF11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.

Methods and devices are provided for activating brown adipose tissue with targeted substance delivery. Generally, the methods and devices can activate BAT to increase thermogenesis, e.g., increase heat production in the patient, which over time can lead to weight loss and / or improved metabolic function. In one embodiment, a chemical configured to stimulate nerves that activate the BAT and / or to stimulate brown adipocytes directly can be delivered to a patient, thereby increasing thermogenesis in the BAT and inducing weight loss and / or improved metabolic function through energy expenditure. The chemical can be delivered to the patient locally and / or systemically to stimulate the nerves and / or the brown adipocytes.

Methods and devices are provided for activating brown adipose tissue with targeted substance delivery. Generally, the methods and devices can activate BAT to increase thermogenesis, e.g., increase heat production in the patient, which over time can lead to weight loss and / or improved metabolic function. In one embodiment, a chemical configured to stimulate nerves that activate the BAT and / or to stimulate brown adipocytes directly can be delivered to a patient, thereby increasing thermogenesis in the BAT and inducing weight loss and / or improved metabolic function through energy expenditure. The chemical can be delivered to the patient locally and / or systemically to stimulate the nerves and / or the brown adipocytes.

Methods and devices are provided for activating brown adipose tissue (BAT) with light. Generally, the methods and devices can activate BAT to increase thermogenesis, e.g., increase heat production in the patient, which over time can lead to weight loss and / or improved metabolic function. In one embodiment, a medical device is provided that activates BAT by using light to stimulate nerves that activate the BAT and / or to stimulate brown adipocytes directly, thereby increasing thermogenesis in the BAT and inducing weight loss and / or improved metabolic function through energy expenditure. The light can be configured to directly or indirectly stimulate the nerves and / or the brown adipocytes. The light can be configured to indirectly stimulate the nerves and / or the brown adipocytes by activating a light activatable medium administered to a patient and configured to respond to the light to cause activation of the brown adipose tissue.

Aspects of the present invention include methods and compositions related to the production and use of pluripotent stem cell-derived clonal embryonic progenitor cell types useful in the generation of cellular components of brown adipocyte tissue for research and therapy relating to applications in obesity, diabetes, and cardiovascular disease.

Brown adipose tissue (“BAT”) progenitor cells and methods for identifying BAT progenitor cells in a population of cells are provided. Methods are also provided for inducing differentiation of BAT progenitor cells into differentiated brown adipocytes, inducing expression or increased activity levels of BAT uncoupling protein-1 (“UCP1”), and for identifying agents capable of inducing differentiation of BAT progenitor cells into brown adipocytes and / or inducing expression or increased activity levels of UCP1. Differentiated brown adipocytes and agents and methods for inducing differentiation of BAT progenitor cells can be used for treatment of or the making of medicaments for the treatment of metabolic diseases or conditions in a patient such as obesity, overweight, impaired glucose tolerance, insulin-resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, metabolic syndrome, and the like. Differentiated brown adipocytes and agents and methods for inducing differentiation of BAT progenitor cells can be used for prevention of hypothermia.

Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.

The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e.g., brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Methods of developing and using cell lines, such as stem cell lines, for therapeutic or cosmetic use. In one embodiment the cell lines are used to treat a wide range of degenerative and metabolic disorders including, but not limited to, obesity, diabetes, hypertension, and cardiac deficiency. Also described are methods of using such cell lines to screen for compounds that play a role in regulating a variety of processes.

The present invention is based in part on the discovery of brown and white fat cell specific surface markers. It has been found that the small amino acid transporter Slca10 / Asc1 is a specific surface marker for white adipocytes and that the ligand-gated ion channel P2X5 and the small amino acid transporter Slc36a2 are specific surface markers for brown adipocytes. Having identified these specific white and brown cell surface markers, the present invention provides compositions and methods suitable for the targeting of any number of agents to a white or brown adipose tissue and the identification and isolation of white or brown adipocytes for any number of uses including therapeutic, screening and diagnostic purposes.

A method for converting animal cells into brown adipose tissue cells is provided that includes transforming the animal cells using an expression vector. The expression vector includes a nucleotide sequence encoding HB-EGF operatively linked to a promoter and a nucleotide sequence encoding ADAM 12 operatively linked to a promoter. Converting animal cells to brown adipose tissue cells can be used to treat obesity or to treat cancer by converting target cells to brown adipose tissue cells.

The present invention addresses the problem of providing: a brown adipocyte; a method for preparing the brown adipocyte; a transplantation material containing a brown adipocyte; a prophylactic or therapeutic agent for various diseases and conditions, which contains a brown adipocyte; and a use. As a means for solving the problem, a method for preparing a brown adipocyte is provided, said method being characterized by comprising culturing a differentiated somatic cell from a mammal in a culture medium in the presence of at least one compound selected from the group consisting of (1) a TGFbeta / SMAD pathway inhibitor, (2) a casein kinase 1 inhibitor, (3) a cAMP inducer and (4) an MEK / ERK pathway inhibitor to convert the somatic cell into a brown adipocyte.

The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and / or uncoupling protein 1 (Thermogenin / Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

The invention discloses a method for constructing a genetic engineering cell strain of an obesity-resistant medicine target point UCP1, and besides, discloses establishing and application of an obesity-resistant medicine high-flux screening model. Mainly a CRISPR / Cas9 system is related and utilized, two unique sgRNAs are designed, luciferase-T2A-tdTomato-WPRE-pA is knocked in after N end ATG of aUCP1 gene of cells, particularly luciferase and tdTomato are knocked in gene sites of immortalization brown fat cells UCP1, a first stably-transfected brown fat cell strain in which luciferase and tdTomato are inserted in a promoter region of the UCP1 is formed, and the first stably-transfected brown fat cell strain is applied to high-flux screening of obesity-resistant medicines, evaluation of the obesity-resistant medicines, evaluation of obesity-resistant active substances of organisms and development of a UCP1 detection reagent kit. The UCP1 is uncoupling protein specifically expressed atbrown fat tissue, and is an obesity-resistant new target point. The construction of the stably-transfected genetic engineering cell strain has important significance in the aspects of applying reportgenes and a high-connotation method, performing high-flux screening on a compound library acutely, accurately and efficiently, and obtaining obesity-resistant medicines capable of promoting thermogenesis and reducing weight.

The invention discloses a method for promoting brown adipose tissue differentiation through SFRP4 and an application. The method comprises treating precursor adipose cells for differentiation by usingSFRP4 active proteins (with different concentrations of 0, 1, 10, 100ng / mL), when the cells grow to 80%, culturing with a cell differentiation induction culture medium I until the cells are fused, adding an induction culture medium II into the cells, inducing for 2-8 days, and replacing the culture medium in the culture bottle with an induction culture medium III, inducing for 2-8 days, observingunder a microscope, after dyeing with oil red O, observing under the microscope again, collecting cells with different differentiation days, extracting total RNA of the cells, detecting expression levels of marker genes UCP-1 and SFRP4 of brown adipose cells by using a real-time quantitative PCR analysis technology after the purity and integrity of the RNA are detected to be qualified, and finally, carrying out statistical analysis. The experimental process is uniform in sampling, and the result reliability is high.

Applications of butylidenephthalide (BP), comprising the use of BP in providing a kit for promoting differentiation of stem cells into brown adipose cells, and the use of BP in preparing a medicament, where the medicament is used for inhibiting the accumulation of white adipose cells, promoting the conversion of white adipose cells into brown adipose cells, inhibiting weight gain and / or reducing the content of triglycerides, glucose, and total cholesterol in blood.

Compositions and methods for producing autologous brown adipose cells in vitro or in vivo are provided. In particular, a drug delivery device is described that recruits adipose stem cells (ASCs) to a site in the body of a subject. These ASCs may then be isolated and induced to differentiate into autologous brown adipose cells. Alternatively, the drug delivery device may also include differentiation factors that induce differentiation of the recruited ASCs into brown adipose cells in vivo. The brown adipose cells produced by these methods may be used therapeutically to treat conditions, such as obesity and diabetes.

A method for converting animal cells into brown adipose tissue cells is provided that includes transforming the animal cells using an expression vector. The expression vector includes a nucleotide sequence encoding HB-EGF operatively linked to a promoter and a nucleotide sequence encoding ADAM 12 operatively linked to a promoter. Converting animal cells to brown adipose tissue cells can be used to treat obesity or to treat cancer by converting target cells to brown adipose tissue cells.

The present invention aims to provide a brown adipocyte and a generation method thereof, a transplantation material containing a brown adipocyte, a prophylactic agent or therapeutic agent containing a brown adipocyte for various diseases and conditions, and use thereof. Provided is a method for generating a brown adipocyte, including converting a differentiated somatic cell of a mammal to a brown adipocyte by culturing the somatic cell in a medium in the presence of at least one kind of a compound selected from the group consisting of (1) a TGFβ / SMAD pathway inhibitor, (2) a casein kinase 1 inhibitor, (3) a cAMP inducer and (4) a MEK / ERK pathway inhibitor.

The invention relates to medical application of long-chain non-coding RNA (LncRNA-266), in particular to application of LncRNA-266 in preparation of a drug for inducing brown adipose cell differentiation, which can promote body energy consumption and resist obesity. Obese mice are treated by the LncRNA-266, and a result shows that the LncRNA-266 can promote differentiation of beige fat cells of the obese mice to brown fat cells and consume body energy, so that weight gain is inhibited. It is further found that the LncRNA-266 can reduce the blood glucose level of obese mice and improve the insulin sensitivity.

Methods of generating functional human brown adipocytes, comprising exposing human stem cells, progenitor cells, or white adipocytes to culture with an differentiation cocktail that comprises one or more browning agents (e.g., one or more macromolecular crowders), and optionally one or more adipogenic agents, are described, as are populations of human brown adipocytes generated by the methods, and uses for the populations. Methods of generating functional human brown adipocytes in an individual, such as by administering a pharmaceutical composition comprising an differentiation cocktail, are also described.

The invention provides novel application of an miR-327 inhibitor and / or an FGF10 accelerant, specifically application to preparation of a medicine for preventing and / or treating fat metabolism syndromes. The miR-327 inhibitor and the FGF10 accelerant both can promote addition of FGF10 in matrix cell compositions of adipose tissue, promote adipose cell precursor of the matrix cell compositions to differentiate to brown adipose cells, promote energy consumption and promote fat metabolism, so that the purpose of preventing and / or treating fat metabolism syndromes is achieved. The invention further provides the medicine for preventing and / or treating fat metabolism syndromes. The medicine comprises the miR-327 inhibitor and pharmaceutically acceptable carriers thereof.

The invention provides a method for treatment of liver cancer in a subject, wherein the method includes that brown adipose cells or compositions thereof are applied to the subject, a drug delivery route of the brown adipose cells is carried out through intratumoral, intraarterial, intravenous, intrapleural, intracystic, intracavitary or abdominal injection or oral administration, and the drug delivery route of the brown adipose cells comprises the step of injecting a brown adipose cell suspension to the subject. The invention also provides a method for constructing a mice liver cancer model, wherein the method comprises the step of reducing or excising brown adipose tissues in mice bodies or reducing brown adipose cells in the mice bodies; preferably, the method comprises the step of carrying out surgical excision or partial excision of the brown adipose tissues in the mice bodies; the invention also provides a method for inhibition of proliferation or metastasis of liver cancer cellsin vivo or in vitro. Inhibition of the liver cancer cells or reduction of metastasis of the liver cancer cells are achieved by contact with the liver cancer cells in vivo or in vitro or mixing with the brown adipose cells.

The subject matter of the invention is a functional population of human brown adipocytes, in which the expression of UCP1, CIDEA, CPT1B and Bc12 is higher, the expression of Bax is lower and the expression of PPAR-alpha, PGC-1alpha, PGC-1 beta and PRDM16 is similar compared with the corresponding expressions of a population of human white adipocytes. The invention also relates to a method for differentiation of hMADS cells into the functional population of human brown adipocytes, to a method for conversion of a population of human white adipocytes into the functional population of human brown adipocytes, and also to a method of screening for molecules capable of modulating the bodyweight in an individual.

The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (Pgd1α) and / or uncoupling protein 1 (Thermogenin / Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

The invention provides a method for treatment of liver cancer in a subject, wherein the method includes that brown adipose cells or compositions thereof are applied to the subject, a drug delivery route of the brown adipose cells is carried out through intratumoral, intraarterial, intravenous, intrapleural, intracystic, intracavitary or abdominal injection or oral administration, and the drug delivery route of the brown adipose cells comprises the step of injecting a brown adipose cell suspension to the subject. The invention also provides a method for constructing a mice liver cancer model, wherein the method comprises the step of reducing or excising brown adipose tissues in mice bodies or reducing brown adipose cells in the mice bodies; preferably, the method comprises the step of carrying out surgical excision or partial excision of the brown adipose tissues in the mice bodies; the invention also provides a method for inhibition of proliferation or metastasis of liver cancer cellsin vivo or in vitro. Inhibition of the liver cancer cells or reduction of metastasis of the liver cancer cells are achieved by contact with the liver cancer cells in vivo or in vitro or mixing with the brown adipose cells.

The present invention provides an anti-obesity agent having an anti-obesity effect obtained by combining a few extracts, which is attained by an anti-obesity agent containing Forsythia leaf extract, Citrus extract, and at least one extract selected from the group consisting of Licorice extract and Gardenia fruit extract, and it is preferable that the anti-obesity agent contains both Licorice extract and Gardenia fruit extract. The anti-obesity agent exhibits an ideal anti-obesity effect for increasing brown adipocytes and muscle weight to increase a basal metabolic rate and to decrease white adipocytes.