Abstract: Angiopoietin-like 4 (Angpt14) is a secreted protein that inhibits lipoprotein lipase (LPL) activity and promotes lipolysis in adipocytes. The present methods provides compositions comprising ANGPTL4 FLD and variants thereof of methods of using such compositions to protect a subject diet-induced obesity without affecting plasma TG levels, and, in an exemplary emobiment improve glucose homeostasis. The invention provides compositions comprising Angpt14 FLD and variants thereof and methods of using these compositions as a therapeutic agent against metabolic diseases, such as obesity and type 2 diabetes.