Figure 1.
ICV administrated hMIC-1/GDF15 induces anorexia and weight loss.
A single injection of 50-1/GDF15 or vehicle was delivered ICV. Changes in body weight (A) and changes in food intake (B) were compared 16 hr post injection. Data expressed as mean ± s.e.m. Abbreviations: BW, body weight; FI, food intake.
Figure 2.
Systemic hMIC-1/GDF15 induces Fos immunoreactivity in brainstem nuclei.
Photomicrographs represent coronal sections (−3.5 mm from interaural line) of Fos immunoreactivity at 30, 60 or 120 min after systemic IP administration of a single dose of hMIC-1/GDF15 or vehicle. Scale bar: 40 µm. Abbreviations: DMX, dorsal motor nucleus of vagus; ap, area postrema; cc, central canal; NTS, nucleus of the solitary tract.
Figure 3.
MIC-1/GDF15 activates both TH-positive and TH-negative neurons.
Photomicrographs of coronal sections through the rostro-caudal span of NTS, demonstrate the distribution of dual Fos (Panel A, green), and TH immunoreactivity (Panel B, red). The merged images are in panel C, scale bar: 40 µm. (D) The Line graph shows the number of neurons that are Fos-positive or Fos and TH-positive in various AP/mNTS regions, identified as mm distance relative to the interaural line. (E-H) The bar graphs show the number of neurons that are immunoreactive to TH, or Fos, or both TH and Fos in mNTS, AP or DMX. Data are presented as mean ± sem. Abbreviations: DMX, dorsal motor nucleus of vagus; ap, area postrema; sp, subpostrema; cc, central canal; NTS, nucleus of the solitary tract; mNTS, medial region of nucleus of the solitary tract.
Figure 4.
Representative Nissl stained sections of AP and mNTS from mice who were (A) Sham operated, (B) AP ablated or (C) AP/NTS ablated. (D) The extent of AP plus NTS lesioning is represented as shaded areas on drawings at four levels of the AP and NTS, which are localised by mm distances from the interaural line.
Figure 5.
The effect of MIC-1/GDF15 on body weight and food intake reduction requires neurons in the AP and/or NTS.
The effect of hMIC-1/GDF15 on mice (A) body weight change and (B) food intake change following ablation of the AP or AP plus NTS or sham surgery. The effect of MIC-1/GDF15 was normalised against the effect on vehicle treated mice for (C) changes in body weight and (D) changes in food intake. Data expressed as mean ± s.e.m. Abbreviations: BW, body weight; FI, food intake.