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Maternal prolactin inhibition causes changes in leptin at 22- and 30-day-old pups
J C Carvalho1, E de Oliveira1, N Peixoto-Silva1
1Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Insights
Inhibiting prolactin during lactation in rats leads to altered leptin levels and metabolic changes, suggesting milk supply impacts long-term obesity risk.
Area of Science:
- Endocrinology
- Metabolic Research
- Developmental Biology
Background:
- Breastfeeding is linked to obesity prevention.
- Previous studies showed prolactin inhibition programs for obesity and metabolic dysfunction.
- Neonatal hyperleptinemia's source and development during nutritional transition require investigation.
Purpose of the Study:
- To investigate the source of neonatal hyperleptinemia.
- To understand how hyperleptinemia develops during the transition from milk to solid food.
- To assess the long-term metabolic consequences of altered prolactin signaling during lactation.
Main Methods:
- Lactating rats were treated with bromocriptine (prolactin inhibitor) or saline during the final days of lactation.
- Measurements included body mass, length, food intake, plasma leptin, adipose tissue leptin mRNA, hypothalamic leptin signaling markers (OBR, STAT3, SOCS3), NPY, glycemia, insulin, cholesterol, HDL-c, and AST.
- Parameters were analyzed at postnatal day 22 (PN22) and PN30.
Main Results:
- Bromocriptine treatment reduced food intake, body mass, and length at PN22, with reduced length and mesenteric fat at PN30.
- Plasma leptin was normal at PN22 but elevated at PN30, with lower adipose leptin mRNA at PN22 and higher mesenteric fat production suggested.
- Hypothalamic leptin sensitivity decreased by PN30, indicated by lower STAT3, higher SOCS3, and increased NPY, alongside altered glycemia and lipid profiles, suggesting liver dysfunction.
Conclusions:
- Neonatal hyperleptinemia, potentially from mesenteric fat, develops during the nutritional transition post-prolactin inhibition.
- Altered leptin signaling and increased NPY in the hypothalamus suggest a programmed resistance to leptin.
- Milk supply plays a critical role in imprinting leptin peaks for nutritional adaptation, and disruptions can lead to long-term metabolic disturbances.
Abstract:
Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and how it develops during the nutritional transition from milk through solid food. Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5 mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food intake, body mass, and body length. At PN30, only body length and mesenteric fat mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue leptin mRNA expression was lower, while plasma leptin was higher in PN30, possibly due to a higher adipose mesenteric tissue production. At PN22, the hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST, suggesting a liver dysfunction. Our data show that milk supply can exert a crucial role in the imprinting of a second leptin peak, which is important for survival adaptation to adverse nutritional conditions.
