Figure 1: MBH oleic acid and VLDL-TG secretion.
(a) Schematic representation of working hypothesis: oleic acid triggers the translocation and activation of PKC-δ and subsequent activation of KATP-channels in the MBH, which activates a neuronal circuit involving NMDA receptors in the DVC and the hepatic vagal nerve, and lowers hepatic VLDL-TG secretion. HFD disrupts MBH oleic acid sensing to regulate VLDL-TG secretion. (b) Experimental protocol for experiments shown (c–l). MBH infusions of vehicle (white open squares, n=6) or oleic acid (black squares; n=8) were commenced at t=−10 min after plasma samples were obtained. Time 0 min plasma samples were obtained after 10 min of MBH infusion, followed by an intravenous injection of tyloxapol (600 mg kg−1). Plasma samples were subsequently obtained every 15 min for the first hour and every 30 min until the end of the experiment at t=150 min. (c) Plasma TG concentrations, (d) rates of appearance of VLDL-TG in plasma (*P<0.05; ** P <0.006 versus vehicle infusion), (e) representative western blots and (f) protein levels of plasma apoB48 and apoB100 (in arbitrary units) following tyloxapol administration with MBH infusion of vehicle or oleic acid (*P<0.03; **P <0.002 versus apoB48 t=0). (g) Body weights on the morning of tyloxapol experiments. Plasma (h) glucose, (i) FFA, (j) insulin, (k) leptin and (l) adiponectin concentrations at t=150 min. Data are presented as mean+s.e.m. Unpaired, two-tailed t-tests were used for the statistical analyses of two groups. For measurements over time, repeated measures analysis of variance was used followed by Duncan’s post hoc test.
