Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation: role of insulin and leptin.
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.
Xu
Jing
J
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006, USA.
Kirigiti
Melissa A
MA
Grove
Kevin L
KL
Smith
M Susan
MS
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000097:blood / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone