Restoration of metabolic inflammation-related ghrelin resistance by weight loss

1. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 1

   Changes in body weight (A), food intake (B) and energy intake (C) of mice fed CD or HFD for 12 weeks. Effects of HFD on ghrelin-induced food intake (D) and energy intake (E) in 1-, 2-, 4-, 8-, or 12-week CD- or HFD-fed mice. Values are means ± s.e.m. n = 6–8. *P < 0.05, **P < 0.01, ***P < 0.001.
2. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 2

   Effect of ghrelin on energy expenditure in DIO mice. Energy expenditure in 2-week CD- (A) or HFD-fed mice (B), and 4-week CD- (C) or HFD-fed mice (D) receiving ghrelin. Values are means ± s.e.m. n = 4–12. *P < 0.05, **P < 0.01, ***P < 0.001.
3. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 3

   Ghsr mRNA expression in the nodose ganglion (A) and hypothalamus (B) of mice fed CD or HFD for 2 (A) or 4 (B) weeks. mRNA levels of Tlr4 (C) in the nodose ganglion of 2- or 4-week CD- or HFD-fed mice. mRNA levels of Iba1, Il-6, and Tnfα in the nodose ganglion and hypothalamus of 2- (D) or 4- (E) week CD- or HFD-fed mice. mRNA levels were normalized against the level of Tbp mRNA (a housekeeping gene) in the same sample, and the normalized values are presented as fold change relative to CD. Values are means ± s.e.m. n = 8–10. *P < 0.05 vs CD.
4. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 4

   mRNA levels of Ap2a, Bhlhe22, and Nrebp in the nodose ganglion (A, B and C) and hypothalamus (D, E and F) of CD- or HFD-fed mice at 12 weeks. mRNA levels were normalized against the level of Tbp mRNA in the same sample. n = 9–14. Values are means ± s.e.m.
5. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 5

   HFD-induced macrophage accumulation in the nodose ganglion and hypothalamus. Representative immunohistochemical detections of Iba1 (red) and NeuN (green) in the nodose ganglion (A, B, C and D) and hypothalamus (F, G, H and I) of 2- or 4-week CD- or HFD-fed mice. Numbers of cells stained with anti-Iba1 antibody in the nodose ganglion (E) and hypothalamus (J). Representative images of Iba1 (green) and CD86 (red) in the nodose ganglion (K, L and M) of 2- or 4-week CD- or HFD-fed mice. Arrows indicate co-localization of CD86 with Iba1. Numbers of CD86-positive cells in the nodose ganglion (N). Histochemical analyses of HSP72 in the hypothalamus of 2-, 4- or 12-week HFD-fed mice (O). Numbers of HSP72-positive cells in the hypothalamus (P). Values are means ± s.e.m. n = 4–5. *P < 0.05, **P < 0.01 vs CD. Scale bars, 50 μm. Dotted lines indicate the third ventricle.
6. View larger version:

   • In this window
   • In a new window

   • Download as PowerPoint Slide

   Figure 6

   Schematic representation of caloric restriction experiment (A). Mice were initially placed on 12-week CD followed by 4 additional weeks of chow (CD), 12-week HFD followed by 4 additional weeks of HFD (HFD), or 12-week HFD followed by switching to chow and caloric restriction to 60% of ad libitum intake (HFD-CR). Body weight, epididymal fat weight, blood glucose, plasma insulin, and ghrelin levels of CD, HFD and HFD-CR mice (B, C, D, E and F). **P < 0.01, ***P < 0.001 vs CD in (B). n = 6–8. Effect of diet change on ghrelin-induced food intake (G). mRNA expression of Ghsr (H) in the nodose ganglion. mRNA levels of Iba1, Tnfα, and Il-6 in the nodose ganglion and hypothalamus of CD, HFD, or HFD-CR mice (I). n = 8–10. Immunohistochemical detections of Iba1 (J), and numbers of cells stained with Iba1 antibody in the nodose ganglion in CD, HFD, and HFD-CR mice (K). n = 4. Values are means ± s.e.m. Iba1, red; NeuN, green. *P < 0.05, **P < 0.01, ***P < 0.001 in (C) to (M). Scale bars, 50 μm.

• © 2018 The authors