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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 weight gain and food intake after 3 day or 3 week high fat diet. (A,E,I,M) Weight gain with 3 day (3D; A,E) and 3 week (3W; I,M) high fat diet (HFD) or chow (CH) in male (A,I) and female (E,M) adult rats that were raised in control (CL) and small (SL) litters. 3D HFD: significant effect of sex [F(1, 48) = 26.77, P < 0.001] and diet [F(1, 48) = 7.16, P = 0.01]. 3W HFD: significant effect of sex [F(1, 50) = 374.35, P < 0.001] and litter size [F(1, 50) = 9.78, P = 0.003]. (B,F,J,N) Food intake with 3D (B,F) and 3W (J,N) HFD in male (B,J) and female (F,N) rats. 3D HFD: significant effect of sex [F(7, 48) = 110.74, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 285.23, P < 0.001] and diet [F(7, 46) = 12.03, P = 0.001]. (C,G,K,O) Energy intake with 3D (C,G) and 3W (K,O) HFG in male (C,K) and female (G,O) rats. 3D HFD: significant effect of sex [F(7, 45) = 88.54, P < 0.001], and diet [F(7, 45) = 53.58, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 266.19, P < 0.001], and diet [F(7, 46) = 93.34 P < 0.001), significant sex × diet interaction [F(7, 46) = 5.54, P = 0.023]. (D,H,L,P) Caloric efficiency with 3D (D,H) and 3W (L,P) HFD in male (D,L) and female (H,P) rats. 3D HFD: significant effect of litter size [F(7, 45) = 6.83, P = 0.012], sex [F(7, 45) = 4.53, P = 0.039], and diet [F(7, 45) = 30.73, P < 0.001], significant litter size × diet interaction [F(7, 45) = 4.45, P = 0.041]. 3W HFD: significant effect of litter size [F(7, 46) = 10.75, P = 0.002], sex [F(7, 46) = 51.85, P < 0.001], and diet [F(7, 46) = 25.39, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
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Figure 2: Effects of neonatal overfeeding on weight gain and food intake after 3 day or 3 week high fat diet. (A,E,I,M) Weight gain with 3 day (3D; A,E) and 3 week (3W; I,M) high fat diet (HFD) or chow (CH) in male (A,I) and female (E,M) adult rats that were raised in control (CL) and small (SL) litters. 3D HFD: significant effect of sex [F(1, 48) = 26.77, P < 0.001] and diet [F(1, 48) = 7.16, P = 0.01]. 3W HFD: significant effect of sex [F(1, 50) = 374.35, P < 0.001] and litter size [F(1, 50) = 9.78, P = 0.003]. (B,F,J,N) Food intake with 3D (B,F) and 3W (J,N) HFD in male (B,J) and female (F,N) rats. 3D HFD: significant effect of sex [F(7, 48) = 110.74, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 285.23, P < 0.001] and diet [F(7, 46) = 12.03, P = 0.001]. (C,G,K,O) Energy intake with 3D (C,G) and 3W (K,O) HFG in male (C,K) and female (G,O) rats. 3D HFD: significant effect of sex [F(7, 45) = 88.54, P < 0.001], and diet [F(7, 45) = 53.58, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 266.19, P < 0.001], and diet [F(7, 46) = 93.34 P < 0.001), significant sex × diet interaction [F(7, 46) = 5.54, P = 0.023]. (D,H,L,P) Caloric efficiency with 3D (D,H) and 3W (L,P) HFD in male (D,L) and female (H,P) rats. 3D HFD: significant effect of litter size [F(7, 45) = 6.83, P = 0.012], sex [F(7, 45) = 4.53, P = 0.039], and diet [F(7, 45) = 30.73, P < 0.001], significant litter size × diet interaction [F(7, 45) = 4.45, P = 0.041]. 3W HFD: significant effect of litter size [F(7, 46) = 10.75, P = 0.002], sex [F(7, 46) = 51.85, P < 0.001], and diet [F(7, 46) = 25.39, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.

Mentions: Neonatal overfeeding did not cause significant differences in the weight gained with the 3D high fat diet in males or females (Figures 2A,E). There were significant effects of sex and diet, with females gaining less weight over the period than males, and those on high fat diet gaining less weight than those on standard rat chow, but there were no differences between relevant groups with post-hoc comparisons. After 3W of high fat diet, all female groups had gained less weight than all male groups. There was also an effect of litter size, with SL gaining more weight than CL but no differences between relevant groups with post-hoc comparisons (Figures 2I,M).


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 weight gain and food intake after 3 day or 3 week high fat diet. (A,E,I,M) Weight gain with 3 day (3D; A,E) and 3 week (3W; I,M) high fat diet (HFD) or chow (CH) in male (A,I) and female (E,M) adult rats that were raised in control (CL) and small (SL) litters. 3D HFD: significant effect of sex [F(1, 48) = 26.77, P < 0.001] and diet [F(1, 48) = 7.16, P = 0.01]. 3W HFD: significant effect of sex [F(1, 50) = 374.35, P < 0.001] and litter size [F(1, 50) = 9.78, P = 0.003]. (B,F,J,N) Food intake with 3D (B,F) and 3W (J,N) HFD in male (B,J) and female (F,N) rats. 3D HFD: significant effect of sex [F(7, 48) = 110.74, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 285.23, P < 0.001] and diet [F(7, 46) = 12.03, P = 0.001]. (C,G,K,O) Energy intake with 3D (C,G) and 3W (K,O) HFG in male (C,K) and female (G,O) rats. 3D HFD: significant effect of sex [F(7, 45) = 88.54, P < 0.001], and diet [F(7, 45) = 53.58, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 266.19, P < 0.001], and diet [F(7, 46) = 93.34 P < 0.001), significant sex × diet interaction [F(7, 46) = 5.54, P = 0.023]. (D,H,L,P) Caloric efficiency with 3D (D,H) and 3W (L,P) HFD in male (D,L) and female (H,P) rats. 3D HFD: significant effect of litter size [F(7, 45) = 6.83, P = 0.012], sex [F(7, 45) = 4.53, P = 0.039], and diet [F(7, 45) = 30.73, P < 0.001], significant litter size × diet interaction [F(7, 45) = 4.45, P = 0.041]. 3W HFD: significant effect of litter size [F(7, 46) = 10.75, P = 0.002], sex [F(7, 46) = 51.85, P < 0.001], and diet [F(7, 46) = 25.39, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
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Related In: Results  -  Collection

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Figure 2: Effects of neonatal overfeeding on weight gain and food intake after 3 day or 3 week high fat diet. (A,E,I,M) Weight gain with 3 day (3D; A,E) and 3 week (3W; I,M) high fat diet (HFD) or chow (CH) in male (A,I) and female (E,M) adult rats that were raised in control (CL) and small (SL) litters. 3D HFD: significant effect of sex [F(1, 48) = 26.77, P < 0.001] and diet [F(1, 48) = 7.16, P = 0.01]. 3W HFD: significant effect of sex [F(1, 50) = 374.35, P < 0.001] and litter size [F(1, 50) = 9.78, P = 0.003]. (B,F,J,N) Food intake with 3D (B,F) and 3W (J,N) HFD in male (B,J) and female (F,N) rats. 3D HFD: significant effect of sex [F(7, 48) = 110.74, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 285.23, P < 0.001] and diet [F(7, 46) = 12.03, P = 0.001]. (C,G,K,O) Energy intake with 3D (C,G) and 3W (K,O) HFG in male (C,K) and female (G,O) rats. 3D HFD: significant effect of sex [F(7, 45) = 88.54, P < 0.001], and diet [F(7, 45) = 53.58, P < 0.001]. 3W HFD: significant effect of sex [F(7, 46) = 266.19, P < 0.001], and diet [F(7, 46) = 93.34 P < 0.001), significant sex × diet interaction [F(7, 46) = 5.54, P = 0.023]. (D,H,L,P) Caloric efficiency with 3D (D,H) and 3W (L,P) HFD in male (D,L) and female (H,P) rats. 3D HFD: significant effect of litter size [F(7, 45) = 6.83, P = 0.012], sex [F(7, 45) = 4.53, P = 0.039], and diet [F(7, 45) = 30.73, P < 0.001], significant litter size × diet interaction [F(7, 45) = 4.45, P = 0.041]. 3W HFD: significant effect of litter size [F(7, 46) = 10.75, P = 0.002], sex [F(7, 46) = 51.85, P < 0.001], and diet [F(7, 46) = 25.39, P < 0.001]. Data are mean + SEM. #Sex difference between corresponding groups. *As indicated, P < 0.05.
Mentions: Neonatal overfeeding did not cause significant differences in the weight gained with the 3D high fat diet in males or females (Figures 2A,E). There were significant effects of sex and diet, with females gaining less weight over the period than males, and those on high fat diet gaining less weight than those on standard rat chow, but there were no differences between relevant groups with post-hoc comparisons. After 3W of high fat diet, all female groups had gained less weight than all male groups. There was also an effect of litter size, with SL gaining more weight than CL but no differences between relevant groups with post-hoc comparisons (Figures 2I,M).

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