'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats.
Exposure to maternal diabetes in utero (GD) may 'program' for obesity. Orexigenic neuropeptides, like neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic neuropeptides, like proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH), are decisively involved in body weight regulation. We investigated consequences of GD and its treatment by pancreatic islet transplantation in rats for development of neuropeptidergic neurons in the arcuate hypothalamic nucleus (ARC) in weanling offspring. In GD, islet transplantation on d15 of pregnancy led to normalized blood glucose. Sham-transplanted GD mothers (TSGD) remained hyperglycemic. Twenty-one-day-old TSGD offspring developed hypothalamic 'malorganization'. Despite of normal leptin and insulin levels in TSGD offspring, increased immunopositivity of NPY and AGRP appeared. TSGD offspring showed unchanged POMC, but decreased MSH-immunopositivity. In conclusion, untreated diabetes in pregnant rats leads to 'malprogramming' of hypothalamic neuropeptidergic neurons in offspring, probably contributing to later development of overweight. These acquired alterations are preventable by treatment of maternal GD.
Franke
Kerstin
K
Clinic of Obstetrics, Division of Experimental Obstetrics, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Harder
Thomas
T
Aerts
Leona
L
Melchior
Kerstin
K
Fahrenkrog
Sonja
S
Rodekamp
Elke
E
Ziska
Thomas
T
Van Assche
F André
FA
Dudenhausen
Joachim W
JW
Plagemann
Andreas
A
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000503:physiopathology*; D001786:Blood Glucose / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D002149:Energy Intake / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D006943:Hyperglycemia / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D009479:Neuropeptides