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Published on: June 24, 2020
Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet
Guohui Cai1, Tara Dinan1, Joanne M Barwood1
1School of Health Sciences and Health Innovations Research Institute, RMIT University Melbourne, VIC, Australia.
Insights
Neonatal overfeeding in rats did not worsen high-fat diet metabolic effects. However, these rats showed a reduced central inflammatory response to a short-term high-fat diet.
Area of Science:
- Neuroscience
- Metabolic Health
- Developmental Biology
Background:
- Neonatal obesity can lead to lifelong obesity and associated health issues.
- Neonatal overfeeding in rats causes persistent weight gain and hypothalamic dysfunction.
- The long-term impact of neonatal overfeeding combined with later-life high-fat diet is not fully understood.
Purpose of the Study:
- To investigate if neonatal overfeeding predisposes rats to exacerbated metabolic and central inflammatory disturbances when exposed to a high-fat diet in adulthood.
- To assess the effects of short-term (3-day) and longer-term (3-week) high-fat diets on metabolic parameters and hypothalamic inflammation in neonatally overfed rats.
Main Methods:
- Rats were neonatally overfed by rearing in small litters.
- In adulthood, rats received normal chow, a high-fat diet for 3 days, or a high-fat diet for 3 weeks.
- Peripheral metabolic indices, hypothalamic microglial changes (central inflammation), and paraventricular nucleus (PVN) responses to lipopolysaccharide (LPS) were measured.
Main Results:
- Neonatal overfeeding did not lead to exacerbated metabolic disturbances or glucose metabolism issues when rats were fed a high-fat diet.
- A short-term high-fat diet increased hypothalamic microglia in control rats, an effect not observed in neonatally overfed rats.
- Neonatally overfed rats exhibited a blunted PVN response to LPS after a short-term high-fat diet, unlike control rats.
Conclusions:
- Neonatal overfeeding does not increase susceptibility to the adverse metabolic effects of a short-term high-fat diet.
- Neonatally overfed rats may have a diminished capacity to respond to central inflammatory challenges, such as LPS, when exposed to a high-fat diet.
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.
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