Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus
Fig 4
Outbred HED-fed Sprague Dawley rats that defend elevated body weights have reduced melanocortin responses.
(A) Weekly mean body weights of outbred Sprague Dawley rats fed HED or chow. Relative to HED-N littermates, some HED-fed animals defend excess body weight (DIO-D), while some are resistant (DR) to HED-induced weight gain (Methods). Asterisks indicate significant weight differences between HED-N and DIO-D (black *) or DR (gray *), respectively, during HED-feeding. When returned to chow for 3 weeks, DR rat weights were not different from those of HED-N rats. (B) Concentration-response relationship of peak MTII effects on IPSCs recorded in mpPVN neurons from HED-N, DR or DIO-D rats. Asterisks indicate significant differences between MTII effects on IPSCs from DIO-D versus HED-N. Arrow indicates effects at 100 nM MTII. (Ci) Peak increase in IPSC amplitude (Δ IPSC) elicited by 100 nM MTII in NS neurons from HED-N, DR and DIO-D rats. MTII effects were not different in neurons from DR and HED-N animals. (Cii) Time course of 100 nM MTII’s effect on IPSC amplitudes recorded in NS neurons from HED-N, DR and DIO-D rats. Asterisks (*) indicate significant differences between IPSC responses in DIO-D versus DR or HED-N. Numbers of neurons studied are indicated in figure legend. Inset, superimposed representative IPSC traces illustrating the MTII effect in an HED-N neuron. (Di) Peak decrease in IPSC amplitude elicited by 300 nM NPY in NS neurons from HED-N, DR and DIO-D rats. NPY effects in HED-N and DIO-D animals did not differ. (Dii) Time course of 300 nM NPY effect on IPSC amplitudes from HED-N, DR and DIO animals. Note that NPY responses from DIO-D and HED-N rats overlap. Asterisks (gray *) indicate significant differences between IPSC responses in DR versus DIO-D or HED-N rats. * p < 0.05, ** p < 0.01, *** p < 0.001.