Changes in morphology and function of adrenal cortex in mice fed a high-fat diet
Changes in morphology and function of adrenal cortex in mice fed a high-fat diet
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DOI：
10.1038/ijo.2014.102
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发表时间：
2014-06
影响因子：
4.9
通讯作者：
Marta Maria Swierczynska;Ivona Mateska;M. Peitzsch;S. R. Bornstein;Trian Chavakis;G. Eisenhofer;V. Lamounier-zepter;Suzanne Eaton
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文献类型：
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作者：
Marta Maria Swierczynska;Ivona Mateska;M. Peitzsch;S. R. Bornstein;Trian Chavakis;G. Eisenhofer;V. Lamounier-zepter;Suzanne Eaton
方法：分别以高脂饮食(HFD)和正常饮食(60%卡路里脂肪和10%卡路里脂肪)喂养动物18周。然后我们评估了肾上腺形态和功能的各个方面，以及基础血浆中类固醇激素和ACTH的浓度。结果：我们发现喂饲HFD的小鼠的肾上腺释放更多的皮质酮和醛固酮，导致血浆水平更高。这种增加是由肾上腺皮质增生和参与类固醇生成的多个基因表达增加推动的。我们证明，饮食诱导的肥胖提高了Gli1阳性前体细胞中的Sonic Hedgehog信号，这些前体细胞填充在肾上腺被膜并产生肾上腺皮质的类固醇生成细胞。随着肾上腺皮质的扩张，用HFD喂养动物会耗尽Gli1阳性祖细胞。结论：这项工作为了解饮食诱导的肥胖如何改变肾上腺的生物学提供了深入的了解。这些变化与Shh信号增加的关联提示了肥胖相关类固醇激素功能障碍的可能治疗策略。
Methods:We fed animals either a high-fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat, respectively) for 18 weeks. We then assessed various aspects of adrenal gland morphology and function, as well as basal plasma concentrations of steroid hormones and ACTH.Results:We show that adrenal glands of mice fed a HFD release more corticosterone and aldosterone, resulting in higher plasma levels. This increase is driven by adrenal cortical hyperplasia, and by increased expression of multiple genes involved in steroidogenesis. We demonstrate that diet-induced obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which populate the adrenal capsule and give rise to the steroidogenic cells of the adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as the adrenal cortex expands.Conclusions:This work provides insight into how diet-induced obesity changes the biology of the adrenal gland. The association of these changes with increased Shh signaling suggests possible therapeutic strategies for obesity-related steroid hormone dysfunction.