Modulators of myocyte lipid accumulation and insulin resistance and methods of use thereof

A method of reducing blood glucose in an obese subject, comprising administering to the subject a pharmaceutical composition comprising

• (i) a compound represented by the general Formula I:
• A-L1-B-L2-D-(R2′)n, Formula I
• wherein
• A is substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted C3-C30 cycloalkyl, unsubstituted C3-C30 cycloalkyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, or unsubstituted alkylthio;
• L1 is —C(O)NR′—, —NR′C(O)—, —C(O)O—, —OC(O)—, —O—, a bond, substituted alkyl, unsubstituted alkyl, substituted alkylene, unsubstituted alkylene, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, or unsubstituted alkylthio;
• L2 is —C(O)NR′—, —NR′C(O)—, —C(O)O—, —OC(O)—, —O—, absent, a bond, substituted alkyl, unsubstituted alkyl, substituted alkylene, unsubstituted alkylene, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, or unsubstituted alkylthio;
• R′ is, for each occurrence, independently hydrogen, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted C3-C30 cycloalkyl, unsubstituted C3-C30 cycloalkyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, or unsubstituted alkylthio;
• B and D are independently substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted C3-C30 cycloalkyl, unsubstituted C3-C30 cycloalkyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, or unsubstituted alkylthio, wherein if L2 is absent and B and D are each independently substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, B and D are a fused ring;
• R2′ is, for each occurrence, independently hydrogen, substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted C3-C30 cycloalkyl, unsubstituted C3-C30 cycloalkyl, substituted heterocyclyl, unsubstituted heterocyclyl, substituted alkyl, unsubstituted alkyl, substituted alkenyl, unsubstituted alkenyl, substituted alkynyl, unsubstituted alkynyl, substituted alkoxy, unsubstituted alkoxy, substituted amino, unsubstituted amino, substituted alkylamino, unsubstituted alkylamino, substituted alkylthio, unsubstituted alkylthio, halogen (F, Cl, Br, I), hydroxyl, nitro, cyano, or two R2′ units fuse to form substituted aryl, unsubstituted aryl, substituted heteroaryl, unsubstituted heteroaryl, substituted C3-C30 cycloalkyl, unsubstituted C3-C30 cycloalkyl, substituted heterocyclyl, or unsubstituted heterocyclyl, and
• wherein n is an integer between 1 and 5, inclusive;
• (ii) a Mondo inhibitor;
• or
• (iii) a combination of (i) and (ii);
• in an effective amount to reduce cellular triacylglycerol (TAG) levels and/or increase cellular glucose uptake in a subject.