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Postnatal development of the ob gene system: elevated leptin levels in suckling fa/fa rats
D V Rayner1, G D Dalgliesh, J S Duncan
1Division of Biomedical Science, Rowett Research Institute, Bucksburn, Aberdeen, United Kingdom.
Insights
The ob gene expresses leptin early in rat postnatal development. In Zucker fa/fa rats, elevated circulating leptin occurs before obesity, indicating early dysregulation of the leptin system.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- The ob gene encodes leptin, a key hormone regulating energy balance and body weight.
- Understanding the early postnatal development of the leptin system is crucial for deciphering obesity pathogenesis.
- Zucker fa/fa rats serve as a valuable model for studying leptin resistance and obesity.
Purpose of the Study:
- To investigate the postnatal expression of the ob gene and leptin production in Zucker fa/fa rats.
- To determine the onset of leptin system dysregulation in relation to the development of the obese phenotype.
- To analyze the temporal relationship between ob mRNA levels, circulating leptin, and adipose tissue development.
Main Methods:
- Analysis of white adipose tissue from rats aged 1 to 28 days.
- Detection of ob mRNA using Northern blotting.
- Quantification of circulating leptin via enzyme-linked immunosorbent assay.
- Genotyping for the fa/fa mutation using polymerase chain reaction and Msp I digestion.
Main Results:
- Ob gene expression (ob mRNA) and leptin production were detected from 1 day of age in both genotypes.
- Circulating leptin levels peaked around 10 days of age and then declined.
- Significantly higher leptin levels were observed in fa/fa rats by 10 days of age, preceding significant changes in adipose tissue mass or ob mRNA levels.
- No significant difference in ob mRNA levels was found between fa/fa and control rats until 25 days of age.
Conclusions:
- The ob gene is expressed and leptin is produced early in postnatal rat life.
- Elevated circulating leptin in suckling fa/fa rats suggests dysregulation of the leptin system occurs before the onset of the overt obese phenotype.
- These findings highlight the early-onset nature of leptin system abnormalities in the Zucker fa/fa rat model.
Abstract:
The postnatal development of the ob gene system has been examined in Zucker fa/fa and +/fa plus +/+ (referred to as +/?) rats. White adipose tissue was taken from animals aged 1 to 28 days. Before weaning, white fat was predominantly subcutaneous, the amount increasing rapidly after birth. ob mRNA was detected by Northern blotting in samples of inguinal fat at 1 day of age and thereafter. Circulating leptin, measured by enzyme-linked immunosorbent assay, was also detectable from 1 day of age, the level rising to a peak by 10 days of age and then declining. The fa/fa genotype was determined from the size of the product after Msp I digestion of the Ob-receptor gene obtained by polymerase chain reaction amplification of genomic DNA. No statistically significant difference in ob mRNA level between fa/fa and +/? animals was obtained before 25 days of age. However, leptin levels were significantly higher in the fa/fa mutant by 10 days of age, despite the absence of any significant elevation in the weight of the major fat depots or in ob mRNA level. It is concluded that the ob gene is expressed and leptin produced early in postnatal life in rats; the elevation of circulating leptin in suckling fa/fa animals indicates that dysregulation of the leptin system occurs before the overt development of the obese phenotype.