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Early maternal hyperleptinemia programs adipogenic phenotype in rats
F Pereira-Toste1, F P Toste, E Oliveira
1Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Insights
Maternal leptin exposure during early lactation programs offspring for obesity and leptin resistance. This early-life exposure leads to increased body weight, higher food intake, and fat mass in adulthood, demonstrating lasting metabolic programming.
Area of Science:
- Endocrinology
- Developmental Biology
- Metabolic Syndrome
Background:
- Maternal nutrition and hormonal exposure during critical developmental windows can influence offspring metabolic health.
- Previous studies indicated leptin treatment late in lactation programs offspring for metabolic dysfunction.
Purpose of the Study:
- To investigate if maternal leptin administration during early lactation programs metabolic dysfunctions in adult offspring.
- To determine the long-term effects of early-life hyperleptinemia on offspring metabolism and leptin sensitivity.
Main Methods:
- Lactating rats were treated with recombinant mouse leptin or saline during the first 10 days of lactation.
- Offspring were monitored for body weight, food intake, and adipose tissue mass until 180 days.
- Adult offspring were tested for their response to leptin injection to assess anorexigenic effects.
Main Results:
- Offspring from leptin-treated mothers exhibited increased body weight gain from day 69 and higher food intake from day 145.
- Adult offspring showed significantly higher visceral adipose tissue, serum glucose, and serum leptin levels.
- Leptin injection failed to reduce food intake in offspring from treated mothers, indicating leptin resistance.
Conclusions:
- Maternal hyperleptinemia during early lactation programs offspring for increased body weight, elevated fat mass, and higher food intake.
- Early-life leptin exposure induces resistance to the anorexigenic effects of leptin in adult offspring.
- These findings highlight the critical role of early-life hormonal environment in long-term metabolic programming.
Abstract:
We have previously reported on the treatment of maternal rats with leptin during the three last days of lactation program for overweight and leptin hypothalamic resistance in the offspring. Here we have investigated whether treatment of maternal rats with leptin in the first ten days of lactation can program metabolic dysfunctions on the adult offspring. Lactating rats were divided into 2 groups: rats (LEP) injected with recombinant mouse leptin (8 microg/100 g/body weight, daily during the first 10 days of lactation) and control group (C) that received the same volume of saline. After weaning, all pups had free access to normal diet, their body weight and food intake were monitored at 4 days interval until 180 days, when they were tested for food intake and response to either leptin (0.5 mg/kg body weight, ip) or saline. The offspring from leptin-treated mothers gained more weight from day 69 onward and had higher food intake from day 145 onward, higher amount of visceral adipose tissue (57%), higher serum glucose (10%), and higher serum leptin (135%) at 180 days compared to control group. The food intake was not reduced as expected after acute injection of leptin in these animals, suggesting resistance to the anorexigenic effect of leptin. We conclude that maternal hyperleptinemia in early lactation programed higher food intake, body weight gain due to higher total and visceral fat mass, and resistance to anorexigenic effect of leptin in the adult offspring even when this hyperleptinemia occurred at the beginning of lactation.
