Negative energy balance during lactation is reflected by low levels of
insulin and
leptin and is associated with chronic
hyperphagia and suppressed
GnRH/LH activity. We studied whether restoration of
insulin and/or
leptin to physiological levels would reverse the lactation-associated
hyperphagia, changes in hypothalamic
neuropeptide expression [increased
neuropeptide Y (NPY) and
agouti-related protein (AGRP) and decreased
proopiomelanocortin (
POMC),
kisspeptin (Kiss1), and
neurokinin B (NKB)] and suppression of LH. Ovariectomized lactating rats (eight pups) were treated for 48 h with sc minipumps containing saline, human
insulin, or rat
leptin. The arcuate nucleus (ARH) was analyzed for NPY, AGRP,
POMC, Kiss1, and NKB
mRNA expression; the dorsal medial hypothalamus (
DMH) was analyzed for NPY
mRNA.
Insulin replacement reversed the increase in ARH NPY/AGRP mRNAs, partially recovered
POMC, but had no effect on recovering Kiss1/NKB.
Leptin replacement only affected
POMC, which was fully recovered.
Insulin/
leptin dual replacement had similar effects as
insulin replacement alone but with a slight increase in Kiss1/NKB. The lactation-induced increase in
DMH NPY was unchanged
after treatments. Restoration of
insulin and/or
leptin had no effect on food intake,
body weight, serum
glucose or serum LH. These results suggest that the negative energy balance of lactation is not required for the hyperphagic drive, although it is involved in the orexigenic changes in the ARH. The chronic
hyperphagia of lactation is most likely sustained by the induction of NPY in the
DMH. The negative energy balance also does not appear to be a necessary prerequisite for the suppression of
GnRH/LH activity.