Gestational weight gain by reduced brain melanocortin activity affects offspring energy balance in rats

Excessive gestational body weight gain of mothers may predispose offspring towards obesity and metabolic derangements. It is difficult to discern the effects of maternal obesogenic factors-such as diet and/or thrifty genetic predisposition-from gestational weight gain per se.

For this reason, genetically normal Wistar rats that were fed regular chow were rendered hypothalamically obese by chronic third-cerebral ventricular (i3vt) infusion during pregnancy and lactation with the melanocortin-3,4 receptor blocker SHU9119. This procedure caused significant increases in body weight gain during pregnancy and lactation compared with controls, and the effects thereof on offspring energy balance and fuel homeostasis were investigated.

At birth, litter weight and size, but not individual pup weight, of SHU9119-treated mothers were significantly smaller than controls. In litters culled to eight, pup weight gain during lactation was only transiently increased by treatment. After weaning, however, male offspring of SHU9119-treated mothers became increasingly heavier over time relative to controls until killing at 9 months. This effect was only transient in females. Increased body weights of males were not associated with disturbances in glucose homeostasis, but with increased energy expenditure instead. Multiple regression analysis revealed that gestational body weight gain, irrespective of the group, contributed positively to increased visceral fat deposition and carbohydrate oxidation in the male offspring. In contrast, the pre-pregnancy body weight of mothers contributed positively to male offspring daily energy expenditure, subcutaneous fat and eviscerated carcass as well as structural organ weights. In female offspring, gestational body weight gain, but not pre-gestational body weight, contributed both to aspects of weight gain as well as to the shift of fat oxidation toward carbohydrate oxidation.

Gestational weight gain induced by low brain melanocortin receptor activity can lead to increased body weight gain in the offspring (particularly in males) independent of obesogenic dietary and/or thrifty genetic predisposition.