Methods and compounds for reducing intracellular lipid storage
Compounds and compositions for reducing intracellular lipid accumulation in a cell are described herein. These compounds are useful for the treatment and prevention of lipid/glycogen disorders, as well as for the treatment and prevention of obesity. A high throughput screen for identifying compounds that reduce intracellular lipid accumulation in cells is also provided.
1. A method for reducing intracellular lipid accumulation in a cell comprising contacting the cell in vitro or in vivo with an effective amount of a compound selected from Table 3, wherein the effective amount of the compound shifts cellular energy metabolism from fatty acid oxidation to glycolysis, thereby reducing intracellular lipid accumulation within the cell, wherein the cell has reduced Adipose Triglyceride Lipase (ATGL) function due to a loss of function mutation in the gene PNPLA2.
2. The method of claim 1 , wherein the cell is selected from the group consisting of: a skeletal muscle cell, a heart muscle cell, a smooth muscle cell, a neuronal cell, a leukocyte cell, a bone marrow cell, an epithelial cell, and an endothelial cell.
3. The method of claim 1 , wherein the contact is in vivo.
4. The method of claim 1 , wherein the compound further comprises a pharmaceutically acceptable carrier.
5. The method of claim 3 , wherein the in vivo contact is in a human subject.
6. The method of claim 3 , wherein the in vivo contact comprises administering the compound using an administration route selected from the group consisting of: oral, subcutaneous, intravenous, intramuscular, intraperitoneal, intranasal, and topical.
7. The method of claim 5 , wherein the human subject has Neutral Lipid Storage Disease associated with myopathy (NLSD-M).
8. The method of claim 1 , wherein the compound is Mefloquine hydrochloride.
9. The method of claim 1 , wherein the effective amount of the compound ranges from about 0.1 μM to about 20 μM.