Eight-week-old male Adn-Lpin1^–/– and WT control mice were fed a 60% HFD for 5 weeks. Five days before clamp, mice were catheterized and allowed to recover. Mice were fasted 5 hours before the clamp procedures as described in detail in Methods. (A) Blood glucose was monitored before and during the clamp and shows that both groups reached and sustained similar steady-state glucose concentrations during the clamp procedure. (B) Exogenous glucose infusion rates (GIR) were measured during the clamp procedure. (C) Endogenous glucose production (rate of appearance [Ra]) was determined from steady-state equations. (D) Whole-body glucose flux (disposal [Rd]) was determined from steady-state equations. (E) High tissue-specific glucose uptake (Rg). (F) Low tissue-specific glucose uptake (Rg). (G) Plasma insulin was measured by radioimmunoassay at –10 minutes for fasting, and 90 and 120 minutes were averaged for clamp values. (H) Ra was plotted against plasma insulin concentrations before and during the clamp. (I) Rd was plotted against plasma insulin concentrations before and during the clamp. (J) Plasma concentrations of non-esterified free fatty acids (NEFA) measured at fasting and clamp and represented as percent suppression from fasting. (K) Plasma concentrations of glycerol measured at fasting and during the clamp and represented as percent suppression from fasting. Data are expressed as means ± SEM, and significance was determined by Student’s t test (A, B, E, F, H, I, J inset, and K inset) or 2-way ANOVA with post hoc Tukey’s multiple-comparison tests where appropriate (C, D, G, J, and K). ^#P < 0.05 for WT vs. Adn-Lpin1^–/– and †P < 0.05 for LFD vs. HFD (n = 5–6).