Accumulation of toxic lipids is the most common etiology of insulin resistance in type 2
diabetes and associated metabolic disorders such as obesity and non-alcoholic fatty liver disease. Understanding
of the underlying mechanisms has revealed various opportunities to target key regulators
in lipid metabolic pathways for the treatment of metabolic diseases. Here, we review the discovery and
development of potential anti-diabetic drugs with primary effects on cellular targets leading to reductions of intracellular
lipids in key organs. We will particularly focus on AMPK, SIRT1, PGC-1α, SREBP-1c, ChREBP, ACC, PPARs and
HSPs which either stimulate in fatty acid oxidation (energy expenditure) or inhibit de novo lipogenesis.