Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

Abstract

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

Figure 1. Body weight during treatment

Body weight during the first 10 days of lactation in pups that received daily leptin injections (•) and pups that received saline (). Values are expressed as means ± s.e.m. of 42 leptin-treated and 30 control pups. *P < 0.05.

Figure 2. Leptinaemia and adrenal catecholamine content at the end of treatment

Serum leptin concentration (A) and catecholamine content (B) in adrenal glands on the 10th day of saline (C) or leptin (L) treatment. Values are expressed as means ± s.e.m. of four control and seven leptin-treated pups during the first 10 days of lactation. *P < 0.05.

Figure 3. Body weight from weaning until adulthood

Body weight from day 21 until day 150 in control ( line) and leptin-treated rats (•). Values are expressed as means ± s.e.m. of 25 control and 29 leptin-treated rats. *P < 0.05.

Figure 4. Adrenal catecholamine content

Catecholamine content in adrenal glands from 150 day old saline- (C) and leptin-treated (L) rats. Data are shown as absolute content (A) and amount relative to gland weight (B). Values are expressed as means ± s.e.m. of nine control and 14 leptin-treated rats.*P < 0.05.

Figure 5. Catecholamine release profile from adrenal medullae of 150-day-old rats

Basal catecholamine secretion is presented at 5, 10 and 15 min. At 20 min, medullae were stimulated with 25 mm caffeine. At 25 and 30 min, medullae were returned to basal conditions. Data are presented relative to adrenal weight and values are expressed as means ± s.e.m. of 12 control () and 14 leptin-treated rats (•). *P < 0.05.

Figure 6. Tyrosine hydroxylase content

Representative blots (A) and optical density (B) of TH protein evaluated by Western blotting in the adrenal medullae at 150 days. Values are expressed as means ± s.e.m. of four control (C) and six leptin-treated (L) rats. *P < 0.05.