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母鼠早期断奶引发肥胖模型内分泌紊乱的发育可塑性。

Developmental plasticity of endocrine disorders in obesity model primed by early weaning in dams.

机构信息

Laboratory of Endocrine Physiology, Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Horm Metab Res. 2013 Jan;45(1):22-30. doi: 10.1055/s-0032-1323703. Epub 2012 Sep 4.

DOI:10.1055/s-0032-1323703
PMID:22948547
Abstract

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRβ3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

摘要

早期断奶与发育可塑性的变化有关。在这里,我们研究了通过早期断奶引发的新生和成年后代的脂肪细胞形态、脂肪组织中脂肪因子的表达或含量以及肾上腺和甲状腺功能。出生后,哺乳期大鼠分为 2 组:EW(早期断奶)-用绷带包裹母鼠以阻止其在哺乳期的最后 3 天内接触到乳汁,而 Control-母鼠的幼崽在整个哺乳期(21 天)内可以自由接触到乳汁。在产后第 21 天,EW 幼崽的内脏和皮下脂肪细胞面积分别降低了 67.7%和 62%,体脂肪量降低了 26%,内脏脂肪细胞中的瘦素表达降低了 64%,但皮下脂肪细胞中的瘦素表达增加了 2.9 倍。肾上腺评估正常,但新生 EW 幼崽的血清 T3 降低了 55%,TSH 降低了 44%。在 180 天,EW 后代表现出更高的食物摄入量、更高的体脂肪量(增加 21.6%)、内脏和皮下脂肪细胞面积(均增加 3 倍)、更高的瘦素(增加 95%)和内脏脂肪组织中的 ADRβ3(增加 2 倍)含量,以及皮下脂肪组织中的脂联素表达增加(增加 47%)但内脏脂肪组织中的表达降低(降低 40%)。成年 EW 后代表现出更高的肾上腺儿茶酚胺含量(增加 31%),但血清皮质酮或甲状腺状态没有变化。因此,早期断奶引发断奶时的甲状腺功能减退症,这可能与成年时脂肪细胞肥大有关。肾上腺儿茶酚胺含量和内脏脂肪细胞 ADRB3 的显著变化通常见于肥胖症,这有助于发展其他心血管和代谢紊乱。

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