Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning
Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning
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DOI：
10.1113/jphysiol.2012.240655
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发表时间：
2012-11-01
影响因子：
5.5
通讯作者：
Trevenzoli, I. H.
中科院分区：
文献类型：
--
作者：
Franco, J. G.;Fernandes, T. P.;Trevenzoli, I. H.
母亲的营养状况影响后代未来的发育。在生命的关键时期（妊娠期或哺乳期），营养不良和营养过剩都可能导致幼犬的激素变化和成年后代的程序性肥胖。我们已经证明，哺乳期高瘦素血症导致成年大鼠中枢性瘦素抵抗、肾上腺儿茶酚胺分泌增加、甲状腺功能亢进、血压和心率升高。在这里，我们评估了母亲等热量高脂肪饮食对母乳成分的影响及其对断奶时后代瘦素血症、能量代谢、肾上腺和甲状腺功能的影响。我们假设，即使在正常热量摄入的情况下，母体饮食中脂肪来源的改变也会扰乱后代的新陈代谢。雌性Wistar大鼠在交配前、妊娠期和哺乳期分别饲喂正常（9%脂肪，C组）和高脂肪（29%脂肪为猪油，HF组）8周。HF母鼠8周后体脂含量升高（+27%,P < 0.05），泌乳结束时体脂含量与对照组相似。因此，HF组母乳中蛋白质（+18%,P < 0.05）、胆固醇（+52%,P < 0.05）和甘油三酯（+86%,P < 0.05）含量较高。断奶时HF子代体重增加（+53%,P < 0.05），肥胖增加（2倍，P < 0.05），这与脂肪组织中β - 3-肾上腺素受体含量降低（-40%,P < 0.05）有关。后代还出现高血糖（+30%,P < 0.05）和高瘦素血症（+62%,P < 0.05）。在下丘脑瘦素信号通路中，我们发现弓形核中P -STAT3/STAT3含量降低（-40%,P < 0.05）， SOCS3含量降低（-55%,P < 0.05），提示瘦素抵抗。HF子代断奶时肾上腺儿茶酚胺含量（+17%,P < 0.05）、肝糖原含量（+50%,P < 0.05）和甲状腺轴亢进均较高。我们的研究结果表明，高脂肪饮食会增加母鼠的体脂，而这种额外的能量会在哺乳期间传递给后代，因为断奶时母鼠的脂肪正常，而幼崽则肥胖。母乳中较高的脂肪和蛋白质浓度似乎会导致HF后代早期营养过剩。除了以脂肪的形式储存能量外，HF后代有更大的糖原储备和高血糖，这可能是由于糖异生增加造成的。高瘦素血症可能刺激肾上腺髓质和甲状腺功能，这可能有助于心血管疾病的发展。这些由母体高脂肪饮食引起的早期变化可能有助于代谢综合征的发展。
Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower beta 3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases maternal body fat and this additional energy is transferred to the offspring during lactation, since at weaning the dams had normal fat and the pups were obese. The higher fat and protein concentrations in the breast milk seemed to induce early overnutrition in the HF offspring. In addition to storing energy as fat, the HF offspring had a larger reserve of glycogen and hyperglycaemia that may have resulted from increased gluconeogenesis. Hyperleptinaemia may stimulate both adrenal medullary and thyroid function, which may contribute to the development of cardiovascular diseases. These early changes induced by the maternal high-fat diet may contribute to development of metabolic syndrome.