Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny.

Neonatal malnutrition is associated with metabolic syndrome in adulthood. Maternal hypoprolactinaemia at the end of lactation (a precocious weaning model) caused obesity, leptin resistance and hypothyroidism in adult offspring, suggesting an association of prolactin (PRL) and programming of metabolic dysfunctions. Metabolic syndrome pathogenesis is still unclear, but abdominal obesity, higher triglycerides, lower high-density lipoprotein (HDL-c) and insulin resistance have been proposed to be important factors involved. We studied the consequences of maternal hypoprolactinaemia during lactation on parameters associated with metabolic syndrome. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg twice a day) or saline on days 19, 20 and 21 of lactation and their offspring were followed from weaning until 180 days old. Adult BRO offspring had higher body weight (+10%, P < 0.05), total body fat (+41%, P < 0.05), visceral fat (+20%, P < 0.05), subcutaneous fat (+3 times, P < 0.05) and total body protein (+24%, P < 0.05). BRO group presented hyperglycaemia (+16%, P < 0.05), lower muscle glycogen (51%, P < 0.05), higher cholesterol (+30%, P < 0.05), higher low-density lipoprotein (LDL-c) (+1.5 times, P < 0.05), higher triglycerides (+49%, P < 0.05), lower HDL-c (28%, P < 0.05), hyperleptinaemia (+2.9 times, P < 0.05), hypoadiponectinaemia (16%, P < 0.05) and hypoprolactinaemia (54%, P < 0.05) as well as higher insulin resistance index (+24%, P < 0.05). Regarding adrenal function, BRO rats showed hypercorticosteronaemia (+46%, P < 0.05) and higher total catecholamine (+37%, P < 0.05). In the hypothalamus, no change was observed in protein expression of the leptin signalling pathway. Thus, neonatal malnutrition induced by maternal PRL inhibition during late lactation programs for obesity, dyslipidaemia and insulin resistance in adult offspring increasing the risk for metabolic syndrome development.