Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats.
In rats selectively bred to develop diet-induced obesity (DIO) or to be diet-resistant (DR), DIO maternal obesity selectively enhances the development of obesity and insulin resistance in their adult offspring. We postulated that the interaction between genetic predisposition and factors in the maternal environment alter the development of hypothalamic peptide systems involved in energy homeostasis regulation. Maternal obesity in the current studies led to increased body and fat pad weights and higher leptin and insulin levels in postnatal day 16 offspring of both DIO and DR dams. However, by 6 wk of age, most of these intergroup differences disappeared and offspring of obese DIO dams had unexpected increases in arcuate nucleus leptin receptor mRNA, peripheral insulin sensitivity, diet- and leptin-induced brown adipose temperature increase and 24-h anorectic response compared with offspring of lean DIO, but not lean DR dams. On the other hand, while offspring of obese DIO dams did have the highest ventromedial nucleus melanocortin-4 receptor expression, their anorectic and brown adipose thermogenic responses to the melanocortin agonist, Melanotan II (MTII), did not differ from those of offspring of lean DR or DIO dams. Thus, during their rapid growth phase, juvenile offspring of obese DIO dams have alterations in their hypothalamic systems regulating energy homeostasis, which ameliorates their genetic and perinatally determined predisposition toward leptin resistance. Because they later go onto become more obese, it is possible that interventions during this time period might prevent the subsequent development of obesity.
Gorski
Judith N
JN
Department of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry, Newark, NJ, USA.
Dunn-Meynell
Ambrose A
AA
Levin
Barry E
BE
D000273:Adipose Tissue; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D004032:Diet; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D054411:Receptors, Leptin; D013997:Time Factors; D015854:Up-Regulation; D015430:Weight Gain
D020738:Leptin; D009479:Neuropeptides; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin