Limits...
Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet.

Cai G, Dinan T, Barwood JM, De Luca SN, Soch A, Ziko I, Chan SM, Zeng XY, Li S, Molero J, Spencer SJ - Front Neurosci (2015)

Bottom Line: The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors.Weight changes and glucose metabolism were unaffected by the early life experience.Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences and Health Innovations Research Institute, RMIT University Melbourne, VIC, Australia.

ABSTRACT
Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat) and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS). Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day) high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

No MeSH data available.


Related in: MedlinePlus

Effects of neonatal overfeeding on hypothalamic microglia after 3 day or 3 week high fat diet. Numbers (A,C,E,G) and density (B,D,F,H) of ionized calcium-binding adapter molecule-1 (Iba-1)-stained cells after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male (A–D) and female (E–H) adult rats that were raised in control (CL) and small (SL) litters. (A,B,E,F) paraventricular nucleus of the hypothalamus (PVN). Microglial number: significant effect of sex [F(11, 68) = 20.53, P < 0.001] and significant litter size × diet × sex interaction [F(11, 68) = 7.06, P = 0.002]. Microglial density: significant effect of litter size [F(11, 68) = 43.68, P = 0.029] and sex [F(11, 68) = 31.96, P < 0.001] and a significant litter size x diet x sex interaction [F(11, 68) = 3.54, P = 0.035]. (C,D,G,H) arcuate nucleus (ARC). Microglial number: significant effect of litter size [F(11, 68) = 5.39, P = 0.023] and sex [F(11, 68) = 7.28, P = 0.009]. There was also an effect of diet of P < 0.06 [F(11, 68) = 2.95, P = 0.059]. Microglial density: significant effect of sex [F(11, 68) = 38.74, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05. (I) Representative photomicrographs of the PVN from male CL chow, SL chow, CL 3D, SL 3D, CL 3W, and SL 3W illustrating differences in numbers and density of Iba-1-stained cells. Scale bar = 1 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4292443&req=5

Figure 6: Effects of neonatal overfeeding on hypothalamic microglia after 3 day or 3 week high fat diet. Numbers (A,C,E,G) and density (B,D,F,H) of ionized calcium-binding adapter molecule-1 (Iba-1)-stained cells after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male (A–D) and female (E–H) adult rats that were raised in control (CL) and small (SL) litters. (A,B,E,F) paraventricular nucleus of the hypothalamus (PVN). Microglial number: significant effect of sex [F(11, 68) = 20.53, P < 0.001] and significant litter size × diet × sex interaction [F(11, 68) = 7.06, P = 0.002]. Microglial density: significant effect of litter size [F(11, 68) = 43.68, P = 0.029] and sex [F(11, 68) = 31.96, P < 0.001] and a significant litter size x diet x sex interaction [F(11, 68) = 3.54, P = 0.035]. (C,D,G,H) arcuate nucleus (ARC). Microglial number: significant effect of litter size [F(11, 68) = 5.39, P = 0.023] and sex [F(11, 68) = 7.28, P = 0.009]. There was also an effect of diet of P < 0.06 [F(11, 68) = 2.95, P = 0.059]. Microglial density: significant effect of sex [F(11, 68) = 38.74, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05. (I) Representative photomicrographs of the PVN from male CL chow, SL chow, CL 3D, SL 3D, CL 3W, and SL 3W illustrating differences in numbers and density of Iba-1-stained cells. Scale bar = 1 mm.

Mentions: In agreement with our previous findings (Ziko et al., 2014), neonatal overfeeding significantly increased PVN microglial numbers so that under chow-fed conditions, male SL rats had more microglia than CL in this region (Figures 6A,I). In males, the 3D high fat diet caused a substantial increase in microglial numbers and density in CL rats but, interestingly, caused a reduction in microglial numbers in SL rats compared with the chow diet (Figures 6A,I). After 3W high fat diet, microglial numbers remained elevated in CL compared with under chow conditions, but there was no effect of the 3W diet on SL rats (Figures 6A,I). Similar trends were seen in microglial density. In this case, the 3D high fat diet increased microglial density in CL but not SL and the 3W high fat diet had little effect (Figure 6B). In females the responses were more ambiguous, with neonatal overfeeding and adult diet having no significant effects (Figures 6E,F).


Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet.

Cai G, Dinan T, Barwood JM, De Luca SN, Soch A, Ziko I, Chan SM, Zeng XY, Li S, Molero J, Spencer SJ - Front Neurosci (2015)

Effects of neonatal overfeeding on hypothalamic microglia after 3 day or 3 week high fat diet. Numbers (A,C,E,G) and density (B,D,F,H) of ionized calcium-binding adapter molecule-1 (Iba-1)-stained cells after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male (A–D) and female (E–H) adult rats that were raised in control (CL) and small (SL) litters. (A,B,E,F) paraventricular nucleus of the hypothalamus (PVN). Microglial number: significant effect of sex [F(11, 68) = 20.53, P < 0.001] and significant litter size × diet × sex interaction [F(11, 68) = 7.06, P = 0.002]. Microglial density: significant effect of litter size [F(11, 68) = 43.68, P = 0.029] and sex [F(11, 68) = 31.96, P < 0.001] and a significant litter size x diet x sex interaction [F(11, 68) = 3.54, P = 0.035]. (C,D,G,H) arcuate nucleus (ARC). Microglial number: significant effect of litter size [F(11, 68) = 5.39, P = 0.023] and sex [F(11, 68) = 7.28, P = 0.009]. There was also an effect of diet of P < 0.06 [F(11, 68) = 2.95, P = 0.059]. Microglial density: significant effect of sex [F(11, 68) = 38.74, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05. (I) Representative photomicrographs of the PVN from male CL chow, SL chow, CL 3D, SL 3D, CL 3W, and SL 3W illustrating differences in numbers and density of Iba-1-stained cells. Scale bar = 1 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4292443&req=5

Figure 6: Effects of neonatal overfeeding on hypothalamic microglia after 3 day or 3 week high fat diet. Numbers (A,C,E,G) and density (B,D,F,H) of ionized calcium-binding adapter molecule-1 (Iba-1)-stained cells after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male (A–D) and female (E–H) adult rats that were raised in control (CL) and small (SL) litters. (A,B,E,F) paraventricular nucleus of the hypothalamus (PVN). Microglial number: significant effect of sex [F(11, 68) = 20.53, P < 0.001] and significant litter size × diet × sex interaction [F(11, 68) = 7.06, P = 0.002]. Microglial density: significant effect of litter size [F(11, 68) = 43.68, P = 0.029] and sex [F(11, 68) = 31.96, P < 0.001] and a significant litter size x diet x sex interaction [F(11, 68) = 3.54, P = 0.035]. (C,D,G,H) arcuate nucleus (ARC). Microglial number: significant effect of litter size [F(11, 68) = 5.39, P = 0.023] and sex [F(11, 68) = 7.28, P = 0.009]. There was also an effect of diet of P < 0.06 [F(11, 68) = 2.95, P = 0.059]. Microglial density: significant effect of sex [F(11, 68) = 38.74, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05. (I) Representative photomicrographs of the PVN from male CL chow, SL chow, CL 3D, SL 3D, CL 3W, and SL 3W illustrating differences in numbers and density of Iba-1-stained cells. Scale bar = 1 mm.
Mentions: In agreement with our previous findings (Ziko et al., 2014), neonatal overfeeding significantly increased PVN microglial numbers so that under chow-fed conditions, male SL rats had more microglia than CL in this region (Figures 6A,I). In males, the 3D high fat diet caused a substantial increase in microglial numbers and density in CL rats but, interestingly, caused a reduction in microglial numbers in SL rats compared with the chow diet (Figures 6A,I). After 3W high fat diet, microglial numbers remained elevated in CL compared with under chow conditions, but there was no effect of the 3W diet on SL rats (Figures 6A,I). Similar trends were seen in microglial density. In this case, the 3D high fat diet increased microglial density in CL but not SL and the 3W high fat diet had little effect (Figure 6B). In females the responses were more ambiguous, with neonatal overfeeding and adult diet having no significant effects (Figures 6E,F).

Bottom Line: The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors.Weight changes and glucose metabolism were unaffected by the early life experience.Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences and Health Innovations Research Institute, RMIT University Melbourne, VIC, Australia.

ABSTRACT
Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat) and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS). Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day) high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

No MeSH data available.


Related in: MedlinePlus