The mismatch between maternal undernutrition and adequate nutrition after birth increases the risk of developing metabolic diseases. We aimed to investigate whether the hyperghrelinemia during maternal undernourishment rewires the hypothalamic development of the offspring and contributes to the conversion to an obese phenotype when fed a high-fat diet (HFD). Pregnant C57BL/6 J, wild type (WT) and ghrelin receptor (GHSR)^−/− mice were assigned to either a normal nourished (NN) group, or an undernutrition (UN) (30% food restricted) group. All pups were fostered by NN Swiss mice. After weaning, pups were fed a normal diet, followed by a HFD from week 9. Plasma ghrelin levels peaked at postnatal day 15 (P15) in both C57BL/6 J UN and NN pups. Hypothalamic Ghsr mRNA expression was upregulated at P15 in UN pups compared to NN pups and inhibited agouti-related peptide (AgRP) projections. Adequate lactation increased body weight of UN WT but not of GHSR^−/− pups compared to NN littermates. After weaning with a HFD, body weight and food intake was higher in WT UN pups but lower in GHSR^−/− UN pups than in NN controls. The GHSR prevented a decrease in ambulatory activity and oxygen consumption in UN offspring during ad libitum feeding. Maternal undernutrition triggers developmental changes in the hypothalamus in utero which were further affected by adequate feeding after birth during the postnatal period by affecting GHSR signaling. The GHSR contributes to the hyperphagia and the increase in body weight when maternal undernutrition is followed by an obesity prone life environment.

产妇营养不足与出生后营养不足之间的不匹配会增加患代谢性疾病的风险。我们的目的是调查母体营养不良期间的高血糖血症是否会改变后代的下丘脑发育，并在喂食高脂饮食（HFD）时有助于转化为肥胖表型。将怀孕的C57BL / 6 J，野生型（WT）和生长素释放肽受体（GHSR）^-/-小鼠分为正常营养（NN）组或营养不良（UN）（30％食物限制）组。所有幼崽均由NN Swiss小鼠饲养。断奶后，给幼犬喂食正常饮食，然后从第9周开始进行HFD。C57BL/ 6 J UN和NN幼犬的血浆生长素释放肽水平在出生后第15天（P15）达到峰值。下丘脑Ghsr与NN幼崽相比，UN幼崽在P15处的mRNA表达上调，并抑制了刺豚鼠相关肽（AgRP）投射。与NN同窝仔相比，充足的泌乳增加了UN WT的体重，但没有增加GHSR ^-/-的体重。与HFD断奶后，WT UN幼仔的体重和食物摄入量高于NN对照，而GHSR ^-/- UN幼仔的体重和食物摄入量更低。GHSR阻止了随意喂养期间联合国后代的活动能力和氧气消耗的减少。孕产妇营养不良引发子宫下丘脑发育变化在出生后，通过影响GHSR信号转导，进一步受到出生后充足喂养的影响。当孕产妇营养不良并易于肥胖时，GHSR会导致食欲亢进和体重增加。