Figure 5. Genetic disruption of neuronal insulin signaling increases whole body lipolytic flux and impairs the switch from fasting to re–feeding.

(A) Schematic representation of the clamp studies in NIRKO mice. Following a 16 hr fast, NIRKO and littermate control mice were subjected to a 110 min 4 mU · kg⁻¹ · min⁻¹ hyperinsulinemic euglycemic clamp study. (B) Baseline and clamp glycerol fluxes as assessed by [²H–5]–glycerol tracer infusion are increased in the NIRKO mice (n ≥ 5 per group). (C) Plasma β–hydroxybutyrate levels are elevated in the NIRKO mice following a 16 hr fasting challenge (n = 9 per group). (D) Depiction of the fasting re–feeding protocol (E) Plasma NEFA levels before and after re–feeding. Insert depicts % suppression of plasma NEFA levels after food intake (n ≥ 7 per group) (F) Plasma insulin before and after re feeding (n ≥ 8 per group) (G) Food intake during re-feeding (n ≥ 9 per group) (H) Bodyweights after fasting (n ≥ 9 per group). All error bars are s.e.m.; * P < 0.05 versus control mice. (See also Fig. S5 and Tab. S1)