'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats

Brain Res. 2005 Jan 21;1031(2):276-83. doi: 10.1016/j.brainres.2004.11.006.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Regulation / physiology*
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / physiopathology*
  • Blood Glucose / physiology
  • Body Weight / physiology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal
  • Eating / physiology
  • Energy Intake / physiology
  • Feeding Behavior / physiology
  • Female
  • Hyperglycemia / physiopathology
  • Male
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptides / metabolism*
  • Obesity / etiology
  • Obesity / physiopathology*
  • Obesity / prevention & control
  • Pregnancy
  • Pregnancy in Diabetics / physiopathology*
  • Pregnancy, Animal
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar


  • Blood Glucose
  • Neuropeptides