Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth.
OBJECTIVE
Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth.


METHODS
Female Sprague-Dawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups.


METHODS
Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR.


RESULTS
Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53+/-0.13 vs 1.05+/-0.21 ng ml(-1); female: 0.33+/-0.09 vs 2.12+/-0.57 ng ml(-1), respectively; both P<0.05). Hypothalamic mRNA expression of NPY, pro-opiomelanocortin, leptin receptor and STAT3 were also significantly lower in pups from obese dams.


CONCLUSIONS
Long-term maternal obesity, together with lower leptin levels in pups from obese dams may contribute to the lower expression of key appetite regulators on day 1 of life, suggesting altered intrauterine neuron development in response to intrauterine overnutrition, which may contribute to eating disorders later in life.
Morris
M J
MJ
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. m.morris@unsw.edu.au
Chen
H
H
D054369:Agouti-Related Protein / Q000032:analysis / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001069:Appetite Regulation; D015415:Biomarkers / Q000032:analysis; D005260:Female; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009478:Neuropeptide Y / Q000032:analysis / Q000235:genetics; D009765:Obesity / Q000378:metabolism*; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
D054369:Agouti-Related Protein; D015415:Biomarkers; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D011333:Pro-Opiomelanocortin