INS and Insulin resistance: In support of the link between mitochondrial efficiency and insulin resistance in skeletal muscle during high-fat feeding are the results showing that the naturally occurring iodothyronine, 3,5-diiodo-L-thyronine (T2) increases mitochondrial proton leak (Lombardi et al., 2007, 2009), thus decreasing mitochondrial efficiency, and when given to high-fat-fed rats is able to reverse high-fat-induced insulin resistance (de Lange et al., 2011; Moreno et al., 2011).