Inhibition of tat activating regulatory DNA-binding protein 43
Described herein are methods for detecting, characterizing, preventing, and treating metabolic diseases, including obesity and obesity-associated disorders such as diabetes.
1. A method for reducing body fat mass in a subject, the method comprising administering to the subject an oligonucleotide molecule that inhibits the expression of Tat activating regulatory DNA-binding protein 43 (TDP-43) to thereby reduce body fat mass in the subject.
2. The method of claim 1 , wherein the subject further has a decreased respiratory exchange ratio.
3. The method of claim 1 , wherein the subject further has increased fat oxidation.
4. The method of claim 1 , wherein the subject further has weight loss.
5. The method of claim 1 , wherein the body fat mass is whole body fat mass.
6. The method of claim 1 , wherein the oligonucleotide is an antisense oligonucleotide that binds to mRNA encoding TDP-43.
7. The method of claim 1 , wherein the oligonucleotide is an siRNA specific for TDP-43.
8. The method of claim 1 , wherein the oligonucleotide is an shRNA specific for TDP-43.
9. A method for reducing body fat mass in a subject, the method comprising administering to the subject an agent that: (i) binds to Tat activating regulatory DNA-binding protein 43 (TDP-43) and (ii) inhibits the ability of TDP-43 to regulate a TDP-43 regulated gene, to thereby reduce body fat mass in the subject.
10. The method of claim 9 , wherein the agent is a small molecule.
11. The method of claim 9 , wherein the agent is a nucleic acid.
12. The method of claim 9 , wherein the agent is an anti-TDP-43 antibody or a non-activating form of TDP-43 polypeptide or fragment thereof.
13. The method of claim 9 , wherein the subject is a human.
14. The method of claim 9 , wherein the subject further has a decreased respiratory exchange ratio.
15. The method of claim 9 , wherein the subject further has increased fat oxidation.
16. The method of claim 9 , wherein the subject further has weight loss.
17. The method of claim 9 , wherein the body fat mass is whole body fat mass.