Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction.
Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction.
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DOI：
10.1152/ajpendo.00229.2021
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发表时间：
2021-11-01
期刊：
影响因子：
--
通讯作者：
Thompson JA
中科院分区：
文献类型：
--
作者：
Mikolajczak A;Sallam NA;Singh RD;Scheidl TB;Walsh EJ;Larion S;Huang C;Thompson JA
本研究确定了子宫内脂肪生成的扰动是否会导致晚年脂肪组织（AT）功能障碍，这是代谢功能障碍的母鼠所生后代心脏代谢风险编程的基础。瘦素受体缺乏症（Hetdb）杂合雌性小鼠的孕前脂肪量是野生型（Wt）的2.4倍，妊娠后期血浆胰岛素和甘油三酯水平高于野生型（P < 0.05）。为了分离宫内环境的作用，对每次妊娠的野生型（Wt）后代进行了研究。分离祖细胞的分化潜力和细胞大小分布分析显示Hetdb母鼠出生的Wt幼崽脂肪生成加速，并伴有新生儿脂肪量的较高积累。成年后，与Wt妊娠相比，Hetdb所生Wt后代的男性（69%）和女性（20%）全身脂肪量更高，同时脂肪细胞肥大和高脂血症（均P < 0.05）。气相色谱脂质组学分析显示，高脂/果糖饮食（HFFD）后，脂肪生成指数（16:0/18:2n6）增加。Hetdb母鼠所生Wt后代餐后胰岛素、ADIPO-IR和体外AT对异丙肾上腺素的溶脂反应均较高（P < 0.05）。宫内代谢刺激可能引导更大比例的祖细胞向终末分化，从而易导致肥大诱导的脂肪细胞功能障碍。新的和值得注意的是，这项研究表明，在围产期脂肪组织发育的窗口期，脂肪的加速形成容易导致晚年肥厚性脂肪细胞功能障碍，从而损害皮下储存的缓冲功能。
This study determined if a perturbation in in utero adipogenesis leading to later life adipose tissue (AT) dysfunction underlies programming of cardiometabolic risk in offspring born to dams with metabolic dysfunction. Female mice heterozygous for the leptin receptor deficiency (Hetdb) had 2.4-fold higher prepregnancy fat mass and in late gestation had higher plasma insulin and triglycerides compared with wild-type (Wt) females (P < 0.05). To isolate the role of the intrauterine milieu, wild-type (Wt) offspring from each pregnancy were studied. Differentiation potential in isolated progenitors and cell size distribution analysis revealed accelerated adipogenesis in Wt pups born to Hetdb dams, accompanied by a higher accumulation of neonatal fat mass. In adulthood, whole body fat mass by NMR was higher in male (69%) and female (20%) Wt offspring born to Hetdb versus Wt pregnancies, along with adipocyte hypertrophy and hyperlipidemia (all P < 0.05). Lipidomic analyses by gas chromatography revealed an increased lipogenic index (16:0/18:2n6) after high-fat/fructose diet (HFFD). Postprandial insulin, ADIPO-IR, and ex vivo AT lipolytic responses to isoproterenol were all higher in Wt offspring born to Hetdb dams (P < 0.05). Intrauterine metabolic stimuli may direct a greater proportion of progenitors toward terminal differentiation, thereby predisposing to hypertrophy-induced adipocyte dysfunction. NEW & NOTEWORTHY This study reveals that accelerated adipogenesis during the perinatal window of adipose tissue development predisposes to later life hypertrophic adipocyte dysfunction, thereby compromising the buffering function of the subcutaneous depot.
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影响因子：
16.2
作者：
Sacks DA;Hadden DR;Maresh M;Deerochanawong C;Dyer AR;Metzger BE;Lowe LP;Coustan DR;Hod M;Oats JJ;Persson B;Trimble ER;HAPO Study Cooperative Research Group
通讯作者：
HAPO Study Cooperative Research Group
影响因子：
4.5
作者：
Cedernaes J;Alsiö J;Västermark A;Risérus U;Schiöth HB
通讯作者：
Schiöth HB
影响因子：
3.3
作者：
Holtrup, Brandon;Church, Christopher D.;Rodeheffer, Matthew S.
通讯作者：
Rodeheffer, Matthew S.
影响因子：
7.7
作者：
Dabelea, D;Hanson, RL;Knowler, WC
通讯作者：
Knowler, WC
DOI：
10.1152/ajpendo.00211.2001
发表时间：
2002-03-01
影响因子：
5.1
作者：
Bassilian, S;Ahmed, S;Lee, WNP
通讯作者：
Lee, WNP