Endocrine Abstracts (2002) 3 P181

Gender differences in the relationship between leptin and the autonomic nervous system

DEH Flanagan1, JC Vaile2, GW Petley3, VM Moore4, IF Godsland5, RA Cockington4, JS Robinson4 & DI Phillips6

1Department of Endocrinology, Derriford Hospital, Plymouth; 2Queen Elizabeth Medical Centre, Birmingham, UK; 3Southampton University Hospitals, Southampton, UK; 4University of Adelaide, Adelaide, South Australia; 5Imperial College School of Medicine, London, UK; 6MRC Environmental Epidemiology Unit, Southampton, UK.

Leptin is a crucial hormone in the regulation of body weight. It is produced by adipose tissue and acts centrally decreasing appetite and increasing energy expenditure. Leptin has been shown to stimulate sympathetic nervous system activity in vitro although the physiological relevance of this remains unclear. Increased sympathetic nervous system (SNS) activity has been implicated in the pathogenesis of insulin resistance and a greatly increased cardiovascular risk. We have therefore investigated whether leptin is associated with cardiac sympatho-vagal activity using spectral analysis of heart rate variability (HRV) in a cohort of 130 young men and women. Insulin sensitivity was assessed using the IVGTT and minimal model. Women showed significantly higher fasting leptin, heart rate, cardiac sympathetic activity and lower insulin sensitivity. Marked gender differences were also seen in the relationship between leptin and cardiac autonomic activity. While men showed an inverse relationship between insulin resistance, heart rate and the sympathovagal ratio of cardiac autonomic tone (r = -0.284 p = 0.014) this was not seen in women. Women however showed a negative correlation between leptin concentrations, heart rate and the sympathovagal ratio (r = -0.329 p = 0.009) (suggesting leptin is associated with increased SNS activity). The association between leptin and the sympathovagal ratio remains significant allowing for body mass index (p = 0.002) or waist to hip ratio (p =0.001).

Although our data support the view that insulin resistance and the SNS are linked this relationship is complex and shows marked gender differences, with leptin acting as an important mediator in women.

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