With respect to the time course of the onset of insulin resistance, it was observed that 3HB culturing induced a relatively rapid ~40% decrease in insulin-stimulated Akt/AS160/S6 phosphorylation within the first 5 h, which was followed by a phase of slower further decrease until a maximum level was reached at ~80% at 25 h (Supplementary Figure S2). The gene discussed is TBC1D4; the disease is Insulin resistance.