Related Experiment Video
Updated: Jun 28, 2026
Segmentation and Measurement of Fat Volumes in Murine Obesity Models Using X-ray Computed Tomography
Published on: April 4, 2012
Obesity after neonatal overfeeding is independent of hypothalamic microgliosis
Alita Soch1, Luba Sominsky1, Simone N De Luca1
1School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
Insights
Neonatal overfeeding in rats causes lasting obesity and primed microglia. Juvenile minocycline treatment reversed microglial priming in the hypothalamus but did not reverse obesity, suggesting obesity is not driven by hypothalamic inflammation.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Early-life metabolic disruptions, such as neonatal overfeeding, can program brain development and lead to long-lasting effects.
- Neonatal overfeeding in rats results in sustained obesity into adulthood and primes hypothalamic and hippocampal microglia, making them hyper-responsive to immune challenges.
- The contribution of microglial priming to obesity and the potential for reversing these effects remain unclear.
Purpose of the Study:
- To investigate whether juvenile minocycline intervention can normalize both microglial priming and obesity in neonatally overfed rats.
- To determine if minocycline treatment can ameliorate the long-term consequences of early-life overfeeding on brain microglia and body weight.
Main Methods:
- Neonatal Wistar rats were assigned to control-fed (litter size 12) or neonatally overfed (litter size 4) groups.
- After weaning, rats received intraperitoneal minocycline injections every other day for 3 weeks (postnatal days 21-42).
- Body composition and microglial profiles were assessed 24 hours after an immune challenge with lipopolysaccharide.
Main Results:
- Neonatal overfeeding led to persistent weight gain, which minocycline treatment failed to reverse.
- Minocycline successfully reversed microglial priming in hypothalamic regions associated with feeding.
- Effects on pro-inflammatory cytokines, microglial number, and morphology in the hippocampus were minimal.
Conclusions:
- Juvenile minocycline intervention can ameliorate the programming effect of neonatal overfeeding on hypothalamic microglial priming.
- Persistent obesity following neonatal overfeeding is likely independent of hypothalamic inflammation and microglial activity.
- These findings suggest that while microglial priming can be modulated, it may not be the primary driver of obesity in this model.
Abstract:
The early-life environment is important in programming brain development, and metabolic disruptions at this time can have long-lasting effects. Previously, we have shown that rats overfed for the first 3 weeks of their neonatal life maintain obesity into adulthood. Neonatal overfeeding also leads to primed hypothalamic and hippocampal microglia that are hyper-responsive to an immune challenge in adulthood. However, whether this microglial priming contributes to the obese phenotype and whether it is possible to reverse either the obesity or the microglial priming are not clear. In the present study, we hypothesised that an intervention with minocycline during the juvenile period (postnatal day 21-42) would normalise both the microglial priming and obesity. To induce obesity in neonatal Wistar rats, we manipulated the litter sizes in which they were suckled, yielding litters of 12 (control-fed) or four (neonatally overfed). After weaning, we administered minocycline i.p. every second day for a 3-week period and examined body composition and microglial profiles 24 hours following an immune challenge with lipopolysaccharide. As demonstrated previously, neonatal overfeeding resulted in prolonged weight gain. However, minocycline failed to reverse this effect. Minocycline did reverse microglial priming in feeding-related regions of the hypothalamus, with minimal effects on pro-inflammatory cytokines and on microglial number and morphology in the hippocampus. Thus, the programming effect of neonatal overfeeding on microglial priming can be ameliorated by minocycline later in life. However, the persistent obesity seen after neonatal overfeeding is likely not driven by changes in hypothalamic inflammation and microglial activity.
Related Concept Videos
01:30Regulation of Food Intake
01:24Obesity