Fat regulation
The present invention provides methods and compounds for regulating fat metabolism and achieving fat homeostasis in a subject. Methods and compound for regulating body weight, reducing body fat, and inducing weight loss are also provided, as are methods and compounds for treating or preventing obesity and for preventing or treating conditions associated with altered fat metabolism including, e.g., obesity, diabetes, atherosclerosis, etc.
1. A method for treating obesity in an obese subject, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound which inhibits a hypoxia inducible factor (HIF) hydroxylase, thereby treating the obesity in the subject.
2. A method for regulating body weight in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound which inhibits a HIF hydroxylase, thereby regulating body weight in the subject.
3. A method for reducing body fat in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound which inhibits a HIF hydroxylase, thereby reducing body fat in the subject.
4. A method for reducing serum triglyceride levels in a subject in need thereof, the method comprising administering to the subject an effective amount of a heterocyclic carboxamide compound which inhibits a HIF hydroxylase, thereby reducing triglyceride levels in the subject.
5. The method of claim 3 , wherein the body fat is visceral fat.
6. The method of claim 3 , wherein the body fat is abdominal fat.
7. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the HIF hydroxylase is a HIF prolyl hydroxylase.
8. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the subject is a mammal.
9. The method of claim 8 , wherein the mammal is a human.
10. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the subject is a human with body mass index (BMI) between 25.0 and 29.9.
11. The method of any one of claim 1 , 2 , 3 , or 4 , wherein subject is a human with a body mass index (BMI) at or above 30.
12. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the subject is a male human with a percentage body fat of greater than 25%.
13. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the subject is a female human with a percentage body fat of greater than 31%.
14. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound is a quinoline carboxamide.
15. The method of claim 14 , wherein the quinoline carboxamide is a quinoline-2-carboxamide.
16. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound is a quinoline carbonyl glycine.
17. The method of claim 16 , wherein the quinoline carbonyl glycine is a quinoline-2-carbonyl glycine.
18. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound is an isoquinoline carboxamide.
19. The method of claim 18 , wherein the isoquinoline carboxamide is an isoquinoline-3-carboxamide.
20. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound is an isoquinoline carbonyl glycine.
21. The method of claim 20 , wherein the isoquinoline carbonyl glycine is an isoquinoline-3-carbonyl glycine.
22. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound a pyridine carboxamide, a pyrimidine carboxamide, a cinnoline carboxamide, or a beta-carboline carboxamide.
23. The method of claim 22 , wherein the pyridine carboxamide is a 3-hydroxypyridine carboxamide.
24. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide compound is selected from the group consisting of a pyridine carbonyl glycine, and a pyrimidine carbonyl glycine.
25. The method of claim 24 , wherein the pyridine carbonyl glycine is a 3-hydroxypyridine carbonyl glycine or a 3-methoxy pyridine carbonyl glycine.
26. The method of claim 4 , wherein the compound is selected from the group consisting of [(7-Chloro-3-hydroxy-quinoline-2-carbonyl)-amino]-acetic acid, [(1-Chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino]-acetic acid, [(4-Hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, [(1-Chloro-4-hydroxy-7-methoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, [(3-Hydroxy-6-isopropoxy-quinoline-2-carbonyl)-amino]-acetic acid, [(3-Hydroxy-pyridine-2-carbonyl)-amino]-acetic acid, and [(7-Benzyloxy-1-chloro-4-hydroxy-isoquinoline-3-carbonyl)-amino]-acetic acid methyl ester.
27. The method of any one of claim 1 , 2 , 3 , or 4 , wherein the heterocyclic carboxamide is a heterocyclic carbonyl glycine selected from the group consisting of a quinoline-2-carboxamide, an isoquinoline-3-carboxamide, a 3-methoxy pyridine carbonyl glycine, a 3-hydroxypyridine carbonyl glycine, and a 5-sulfonamidocarbonyl pyridine carboxylate.