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Published on: October 25, 2019
Experimental hyperleptinemia in neonatal rats leads to selective leptin responsiveness, hypertension, and altered
Anne-Maj Samuelsson1, James Clark, Olena Rudyk
1Division of Women's Health, Women's Health Academic Centre, London SE1 7EH, United Kingdom. Anne-Maj.Samuelsson@kcl.ac.uk
Insights
Neonatal exposure to high leptin levels in rats permanently alters cardiovascular function, leading to hypertension and impaired cardiac structure and function in offspring. This highlights the critical impact of early life environment on long-term health.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Endocrinology
Background:
- Maternal obesity is rising, negatively impacting offspring cardiovascular and metabolic health.
- Previous studies linked offspring hypertension to maternal obesity and neonatal hyperleptinemia.
- The direct causal role of neonatal hyperleptinemia requires further investigation.
Purpose of the Study:
- To test the hypothesis that neonatal exposure to elevated leptin levels causally influences offspring cardiovascular function.
- To investigate the long-term effects of early-life hyperleptinemia on blood pressure, cardiac structure, and function.
Main Methods:
- Lean Sprague-Dawley rat pups received twice-daily leptin or saline injections from postnatal day 9 to 15.
- Cardiovascular parameters were assessed using radiotelemetry at 30 days, 2 months, and 12 months.
- Cardiac structure and function were evaluated via echocardiography and isolated heart studies.
Main Results:
- Leptin-treated juvenile rats exhibited increased heart weight and elevated systolic blood pressure.
- Enhanced pressor responses to stress and leptin challenge were observed in leptin-treated rats.
- Altered cardiac structure, impaired systolic function, and heightened sympathetic tone persisted into adulthood.
Conclusions:
- Neonatal hyperleptinemia permanently programs adverse cardiovascular outcomes in offspring.
- Early-life exposure to elevated leptin influences blood pressure regulation and cardiac integrity.
- These findings underscore the importance of managing maternal metabolic health during pregnancy.
Abstract:
The prevalence of obesity among pregnant women is increasing. Evidence from human cohort studies and experimental animals suggests that offspring cardiovascular and metabolic function is compromised through early life exposure to maternal obesity. Previously, we reported that juvenile offspring of obese rats develop sympathetically mediated hypertension associated with neonatal hyperleptinemia. We have now addressed the hypothesis that neonatal exposure to raised leptin in the immediate postnatal period plays a causal role. Pups from lean Sprague-Dawley rats were treated either with leptin (3 mg/kg IP) or with saline twice daily from postnatal day 9 to 15 to mimic the exaggerated postnatal leptin surge observed in offspring of obese dams. Cardiovascular function was assessed by radiotelemetry at 30 days, and 2 and 12 months. In juvenile (30 days) leptin-treated rats, hearts were heavier and night-time (active period) systolic blood pressure was raised (mm Hg; mean ± SEM: male leptin-treated, 132 ± 1 versus saline-treated, 119 ± 1, n=6, P<0.05; female leptin-treated, 132 ± 2 versus saline-treated, 119 ± 1, n=6, P<0.01), and the pressor response to restraint stress and leptin challenge increased compared with saline-treated rats. Heart rate variability demonstrated an increased low:high frequency ratio in 30-day leptin-treated animals, indicative of heightened sympathetic efferent tone. Echocardiography showed altered left ventricular structure and systolic function in 30-day female leptin versus saline-treated rats. These disorders persisted to adulthood. In isolated hearts, contractile function was impaired at 5 months in male leptin-treated rats. Exogenously imposed hyperleptinemia in neonatal rats permanently influences blood pressure and cardiac structure and function.
