Method for selectively inhibiting ACAT1 in the treatment of obesity, metabolic syndrome, and atherosclerosis
The present invention features methods for preventing and treating three related diseases, diet-induced obesity, metabolic syndrome, and atherosclerosis, alone or in combination by inhibiting Acyl-CoA:Cholesterol Acyltransferase 1 (ACATI) activity or expression in myeloid cells.
1. A method for treating diet-induced obesity in a subject comprising contacting myeloid cells of a subject with a Acyl-CoA:Cholesterol Acyltransferase 1 (ACAT1)-selective inhibitor, wherein the ACAT1-selective inhibitor exhibits an IC 50 value that is at least two-fold lower than the corresponding IC 50 value for ACAT2, thereby treating diet-induced obesity in the subject.
2. The method of claim 1 , wherein contacting myeloid cells of a subject with a Acyl-CoA: Cholesterol Acyltransferase 1-selective inhibitor increases insulin sensitivity, lowers circulating levels of adipocytokines, decreases numbers of infiltrating macrophages in adipose tissue and/or decreases fat cell size.
3. The method of claim 1 , wherein the inhibitor inhibits the expression or activity of Acyl-CoA: Cholesterol Acyltransferase 1.
4. The method of claim 1 , wherein the Acyl-CoA:Cholesterol Acyltransferase 1-selective inhibitor is formulated in a liposome, nanoparticle or exosome.
5. The method of claim 4 , wherein the liposome, nanoparticle or exosome is modified with a moiety to target macrophages.