Figure 3. Acetate effects in the hypothalamus.

(a) Regions of interest (ROIs) used in manganese-enhanced MRI (MEMRI). MR image showing the ROI locations in the hypothalamus from which signal intensity (SI) measurements were determined. ARC, arcuate nucleus; VMH, ventromedial hypothalamus; ArP, area postrema; NTS, nucleus of solitary tract. White bar represents 1 mm. (b–e) Hypothalamic neuronal activation in the ARC, VMH, the PVN and the NTS of mice following i.p. administration of acetate or a saline control as determined by MEMRI. Arrow signifies start of i.v. MnCl₂infusion. SI is significantly increased in the ARC of acetate treated mice compared with saline-injected controls based on generalized estimated equations (GEE) and Mann–Whitney U-test; **P<0.01 (n=4–5 per group). (f) Effect of acetate on hypothalamic expression of POMC, NPY and AgRP as determined by hypothalamic qPCR. Data expressed as fold change in expression compared with saline-injected controls at 30 and 60 min post administration one-way ANOVA with post hoc Dunnett’s correction; **P<0.01, ***P<0.001 (n=5 per group). (g,h) pACC and pAMPK hypothalami content expressed in relation to β-actin control, based on two-sided, unpaired Student’s t-test; *P<0.05 (n=5). (i) Immunoblots of hypothalamic pAMPK and pACC levels in mice 30 min after the i.p. injection of either saline or acetate (full blot with annotation available in Supplementary Fig. 1). (j) Proposed mechanism of acetate induced inhibition of the feeding impulse. Relatively increased hypothalamic TCA cycle activity increases ATP production, decreases AMP levels and AMPK inhibition of acetyl-CoA carboxylase (ACC), increases malonyl-CoA levels and stimulates POMC mRNA expression, and inhibits appetite.