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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 peripheral inflammatory gene expression after 3 day or 3 week high fat diet. Liver and fat TLR4 (A–D), NFκ B (E–H), interleukin (IL)-10 (I–L), TNFα (M–P), IL-1β (Q–T) and IL-6 (U–X) after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male and female adult rats that were raised in control (CL) and small (SL) litters. Liver TLR4: significant effect of diet [F(11, 60) = 18.71, P < 0.001] and sex [F(11, 60) = 8.25, P = 0.006], significant litter size × sex interaction [F(11, 60) = 7.47, P = 0.008], significant diet x sex interaction [F(11, 60) = 3.39, P = 0.04]. Liver NFκ B: significant effect of sex [F(11, 56) = 4.12, P = 0.047]. Male fat NFκ B: significant effect of litter size [F(5, 33) = 14.80, P = 0.001]. Liver IL-10 significant effect of sex [F(11, 57) = 11.25, P = 0.001]. Male fat IL-10 significant effect of diet [F(5, 30) = 4.81, P = 0.015]. Liver IL-1β significant effect of sex [F(11, 59) = 26.42, P < 0.001]. Male fat IL-1β significant effect of diet [F(5, 30) = 3.29, P = 0.051]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
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Figure 5: Effects of neonatal overfeeding on peripheral inflammatory gene expression after 3 day or 3 week high fat diet. Liver and fat TLR4 (A–D), NFκ B (E–H), interleukin (IL)-10 (I–L), TNFα (M–P), IL-1β (Q–T) and IL-6 (U–X) after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male and female adult rats that were raised in control (CL) and small (SL) litters. Liver TLR4: significant effect of diet [F(11, 60) = 18.71, P < 0.001] and sex [F(11, 60) = 8.25, P = 0.006], significant litter size × sex interaction [F(11, 60) = 7.47, P = 0.008], significant diet x sex interaction [F(11, 60) = 3.39, P = 0.04]. Liver NFκ B: significant effect of sex [F(11, 56) = 4.12, P = 0.047]. Male fat NFκ B: significant effect of litter size [F(5, 33) = 14.80, P = 0.001]. Liver IL-10 significant effect of sex [F(11, 57) = 11.25, P = 0.001]. Male fat IL-10 significant effect of diet [F(5, 30) = 4.81, P = 0.015]. Liver IL-1β significant effect of sex [F(11, 59) = 26.42, P < 0.001]. Male fat IL-1β significant effect of diet [F(5, 30) = 3.29, P = 0.051]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.

Mentions: We have previously reported neonatal overfeeding influences peripheral and central immune profiles (Clarke et al., 2012; Ziko et al., 2014). We therefore tested if neonatal overfeeding exacerbates the peripheral and central response of inflammatory markers to high fat diet. In the liver there was an increase in TLR4 mRNA after 3D high fat diet in both CL and SL males compared with their chow-fed counterparts. Interestingly, this increase in TLR4 did not persist, but had returned toward baseline values after 3W (Figure 5A). There were no significant differences between the female groups with post-hoc tests and no sex differences, but CL females did show a tendency to have elevated TLR4 after 3D high fat diet compared with chow-fed females (Figure 5B).


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 peripheral inflammatory gene expression after 3 day or 3 week high fat diet. Liver and fat TLR4 (A–D), NFκ B (E–H), interleukin (IL)-10 (I–L), TNFα (M–P), IL-1β (Q–T) and IL-6 (U–X) after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male and female adult rats that were raised in control (CL) and small (SL) litters. Liver TLR4: significant effect of diet [F(11, 60) = 18.71, P < 0.001] and sex [F(11, 60) = 8.25, P = 0.006], significant litter size × sex interaction [F(11, 60) = 7.47, P = 0.008], significant diet x sex interaction [F(11, 60) = 3.39, P = 0.04]. Liver NFκ B: significant effect of sex [F(11, 56) = 4.12, P = 0.047]. Male fat NFκ B: significant effect of litter size [F(5, 33) = 14.80, P = 0.001]. Liver IL-10 significant effect of sex [F(11, 57) = 11.25, P = 0.001]. Male fat IL-10 significant effect of diet [F(5, 30) = 4.81, P = 0.015]. Liver IL-1β significant effect of sex [F(11, 59) = 26.42, P < 0.001]. Male fat IL-1β significant effect of diet [F(5, 30) = 3.29, P = 0.051]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
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Figure 5: Effects of neonatal overfeeding on peripheral inflammatory gene expression after 3 day or 3 week high fat diet. Liver and fat TLR4 (A–D), NFκ B (E–H), interleukin (IL)-10 (I–L), TNFα (M–P), IL-1β (Q–T) and IL-6 (U–X) after 3 day (3D) and 3 week (3W) high fat diet or chow (CH) in male and female adult rats that were raised in control (CL) and small (SL) litters. Liver TLR4: significant effect of diet [F(11, 60) = 18.71, P < 0.001] and sex [F(11, 60) = 8.25, P = 0.006], significant litter size × sex interaction [F(11, 60) = 7.47, P = 0.008], significant diet x sex interaction [F(11, 60) = 3.39, P = 0.04]. Liver NFκ B: significant effect of sex [F(11, 56) = 4.12, P = 0.047]. Male fat NFκ B: significant effect of litter size [F(5, 33) = 14.80, P = 0.001]. Liver IL-10 significant effect of sex [F(11, 57) = 11.25, P = 0.001]. Male fat IL-10 significant effect of diet [F(5, 30) = 4.81, P = 0.015]. Liver IL-1β significant effect of sex [F(11, 59) = 26.42, P < 0.001]. Male fat IL-1β significant effect of diet [F(5, 30) = 3.29, P = 0.051]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
Mentions: We have previously reported neonatal overfeeding influences peripheral and central immune profiles (Clarke et al., 2012; Ziko et al., 2014). We therefore tested if neonatal overfeeding exacerbates the peripheral and central response of inflammatory markers to high fat diet. In the liver there was an increase in TLR4 mRNA after 3D high fat diet in both CL and SL males compared with their chow-fed counterparts. Interestingly, this increase in TLR4 did not persist, but had returned toward baseline values after 3W (Figure 5A). There were no significant differences between the female groups with post-hoc tests and no sex differences, but CL females did show a tendency to have elevated TLR4 after 3D high fat diet compared with chow-fed females (Figure 5B).

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