Materials and methods for the treatment or prevention of obesity

• US 7,704,979 B2
• Filed: 12/14/2001
• Issued: 04/27/2010
• Est. Priority Date: 09/01/2000
• Status: Expired due to Fees

• Current Assignee: University of Tennessee Research Foundation (University of Tennessee)
• Original Assignee: University of Tennessee Research Foundation (University of Tennessee)
• Inventors: Shi, Hang, Zemel, Michael B.
• Primary Examiner(s): Richter; Johann R
• Assistant Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US10/017,568
• Publication Number:
  US 20020192264A1
• Time in Patent Office: 3,056 Days
• Field of Search: 514/909, 514/143.1, 514738- 39, 514/844, 514/952, 514/167, 514/168, 514/729, 530/388.22, 424/401, 424/63
• US Class Current: 514/167
• CPC Class Codes: A23L 33/16 Inorganic salts, minerals or trace elements
• CPC Class Codes: A23L 33/30 Dietetic or nutritional methods, e.g. for losing weight A23L33/10 takes precedence
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents

Abstract

The subject invention provides methods of inducing the loss of adipose tissue by providing a diet high in calcium. In one aspect of the invention, the calcium is provided in the form of dairy products. In yet another aspect of the invention, calcium is provided in the form of a dietary supplement, such as calcium carbonate, of vitamin supplements. Methods of suppressing [Ca²⁺]_i levels in individuals are also provided. The subject invention also provides methods of stimulating lipolysis, inhibiting lipogenesis, and increasing the expression of white adipose tissue uncoupling protein 2 (UPC2). The subject invention also provides methods of increasing the core temperature of an individual.

Claims

1. A method of regulating body weight comprising administering to an individual in need thereof an antagonist of calcitrophic hormone (1,25-(OH)₂-D) activity, wherein the antagonist is 1-β

,25-dihydroxyvitamin D, in an amount effective to block calcitrophic hormone (1,25-(OH)₂-D) activity in adipocytes of said individual, and increase intracellular calcium, said antagonist inducing weight loss, and/or increasing metabolic consumption of adipose tissue.

2. The method of claim 1, wherein the individual has Grade I obesity.

3. The method of claim 1, wherein the individual has Grade II obesity.

4. The method of claim 1, wherein the individual has Grade III obesity.

5. The method of claim 1, wherein the antagonist is contained in a liquid.

6. The method of claim 1, wherein the calcitrophic hormone activity in adipocytes that is blocked is selected from one or more of inhibiting lipolysis, stimulating lipogenesis, increasing adiposity, stimulating triglyceride accumulation, increasing intracellular calcium concentration ([Ca²⁺]_i), inhibiting adipocyte uncoupling protein 2 (UCP2) expression and/or stimulating fatty acid synthase (FAS) activity.

7. The method of claim 1, wherein the antagonist reduces the risk of an obesity related health problem selected from the group consisting of coronary artery disease, stroke, diabetes, osteoarthritis, ligament injuries, perineal dermatitis, diabetes mellitus, cardiomyopathy, and urologic syndrome.

8. The method of claim 1, wherein the individual is a human.

9. The method of claim 1, wherein the individual is a non-human animal.

10. The method of claim 1, wherein the antagonist brings about an effect selected from the group consisting of suppressing adiposity, inhibiting triglyceride accumulation, reducing intracellular calcium concentration ([Ca²⁺]_i, increasing adipocyte uncoupling protein 2 (UCP2) expression, increasing core temperature, accelerating weight loss and fat mass reduction in an individual under caloric restriction, and combinations thereof.

11. The method of claim 1, wherein the antagonist suppresses or decreases intracellular calcium concentration ([Ca²⁺]_i).

12. The method of claim 1, wherein the antagonist blocks the action of 1,25-(OH)2-D in adipocytes.

13. The method of claim 1, wherein the administering decreases the levels of calcitrophic hormones in the adipocytes.

14. The method of claim 1, wherein the antagonist stimulates lipolysis and inhibits lipogenesis.

15. The method of claim 1, wherein the antagonist blocks calcitrophic hormone induced inhibition of lipolysis in adipocytes.

16. The method of claim 1, wherein the antagonist suppresses adiposity and inhibits triglyceride accumulation by stimulating lipolysis and inhibiting lipogenesis.

17. The method of claim 1, wherein the antagonist increases core temperature.

18. The method of claim 1, wherein the antagonist induces a metabolic state in which the energy metabolism is shifted from energy storage to energy expenditure.

19. The method of claim 1, wherein the antagonist accelerates weight loss and/or fat mass reduction in an individual under caloric restriction.