Postnatal exercise protects offspring from high-fat diet-induced reductions in subcutaneous adipocyte beiging in C57Bl6/J mice.
Postnatal exercise protects offspring from high-fat diet-induced reductions in subcutaneous adipocyte beiging in C57Bl6/J mice.
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DOI：
10.1016/j.jnutbio.2021.108853
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发表时间：
2022-01
影响因子：
5.6
通讯作者：
Roemmich, James N.
中科院分区：
文献类型：
--
作者：
Claycombe-Larson, Kate J.;Bundy, Amy;Lance, Elizabeth Black;Darland, Diane C.;Casperson, Shanon L.;Roemmich, James N.
关键词：
母体低蛋白和产后高脂肪（HF）饮食通过增加G9a蛋白（组蛋白3赖氨酸二甲基转移酶）的表达，通过表观遗传降低米色脂肪细胞（BAs），从而控制后代肥胖和2型糖尿病（T2DM）的风险，G9a蛋白是BA标志物成纤维细胞生长因子21 （FGF21）的抑制剂。相反，后代运动可以减少脂肪量和白色脂肪细胞，但其机制尚不清楚。这项工作调查了运动是否通过调节G9a和FGF21的表达来降低由母体HF饮食引起的后代肥胖和2型糖尿病风险，G9a和FGF21的表达可将白色转化为BA。2月龄雌性C57Bl/6J小鼠（F0）在繁殖前3个月饲喂16%（正常脂肪；NF）或45% HF的饲粮，随后进行妊娠和哺乳。雄性后代（F1）被喂食相同的NF和HF饮食，并进一步分为久坐组(S)或自愿轮跑组（Ex），再持续3个月，形成8组：NF（母体治疗组）-NF-S（断奶后治疗组）、NF-HF-S、NF-NF-Ex、NF-HF-Ex、HF-NF-S、HF-HF-S、HF-NF-Ex和HF-HF-Ex。收集皮下脂肪组织，分析FGF21、过氧化物酶体增殖物激活受体- γ辅助激活因子（PGC-1 α， FGF21的诱导因子）、G9a、E4BP4 （G9a辅助激活因子）的蛋白和mRNA表达，以及H3K9去甲基化酶（KDM4C）的蛋白表达。无论母亲饮食和产后运动如何，产后HF饮食均可降低FGF21阳性BA数。在久坐条件下，与NF饮食相比，出生后HF饮食增加了FGF21转录抑制剂G9a和E4BP4的蛋白表达，导致FGF21表达降低。与NF相比，产后HF饮食和运动降低了G9a和E4BP4蛋白的表达，同时降低了FGF21的表达。运动条件下，出生后HF饮食诱导KDM4C蛋白表达，而久坐条件下，出生后HF饮食诱导KDM4C蛋白表达无变化。这些结果表明，产后饮食对后代肥胖和BA数量的影响大于母体饮食。这些数据还表明，后代运动诱导KDM4C，以抵消母体和产后HF饮食引发的G9a增加。未来的研究需要确定KDM4C是否诱导G9a的甲基化状态，从而改变BA的产热功能。
Maternal low-protein and postnatal high-fat (HF) diets program offspring obesity and type 2 diabetes mellitus (T2DM) risk by epigenetically reducing beige adipocytes (BAs) via increased G9a protein expression (Histone3 Lysine9 dimethyl transferase), an inhibitor of the BA marker fibroblast growth factor 21 (FGF21). Conversely, offspring exercise reduces fat mass and white adipocytes, but the mechanisms are not yet understood. This work investigated whether exercise reduces offspring obesity and T2DM risk caused by a maternal HF diet via regulation of G9a and FGF21 expression that would convert white to BA. Two-month-old female C57Bl/6J mice (F0) were fed a 16% (normal fat; NF) or a 45% HF diet for 3 months prior to breeding, and subsequent gestation and lactation. Male offspring (F1) were fed the same NF and HF diets and further divided into either sedentary (S) or voluntary wheel running (Ex) groups for an additional 3 months yielding eight groups: NF (maternal treatment condition)-NF-S (postweaning treatment conditions), NF-HF-S, NF-NF-Ex, NF-HF-Ex, HF-NF-S, HF-HF-S, HF-NF-Ex, and HF-HF-Ex. Subcutaneous adipose tissue was collected for protein and mRNA analysis of FGF21, peroxisome proliferator-activated receptor-gamma coactivator (PGC-1 alpha, inducer of FGF21), G9a, E4BP4 (G9a coactivator), and protein expression of H3K9 demethylases (KDM4C). Postnatal HF diet decreased FGF21 positive BA numbers regardless of maternal diets and postnatal exercise. Under sedentary conditions, postnatal HF diet increased protein expression of FGF21 transcription inhibitors G9a and E4BP4 compared to NF diet resulting in decreased FGF21 expression. In contrast, postnatal HF diet and exercise decreased G9a and E4BP4 protein expression while decreasing FGF21 expression compared to NF diet. Under exercised condition, postnatal HF diet-induced KDM4C protein expression while no changes in KDM4C protein expression were induced by postnatal HF diet under sedentary conditions. These findings suggest that the postnatal diet exerts a greater impact on offspring adiposity and BA numbers than maternal diets. These data also suggest that offspring exercise induces KDM4C to counter the increase in G9a that was triggered by maternal and postnatal HF diets. Future studies need to determine whether KDM4C induces methylation status of G9a to alter thermogenic function of BA.
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影响因子：
5.6
作者：
Claycombe-Larson, Kate G.;Bundy, Amy N.;Roemmich, James N.
通讯作者：
Roemmich, James N.
影响因子：
4.2
作者：
Claycombe, Kate J.;Uthus, Eric O.;Johnson, W. Thomas
通讯作者：
Johnson, W. Thomas
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cohen P;Levy JD;Zhang Y;Frontini A;Kolodin DP;Svensson KJ;Lo JC;Zeng X;Ye L;Khandekar MJ;Wu J;Gunawardana SC;Banks AS;Camporez JP;Jurczak MJ;Kajimura S;Piston DW;Mathis D;Cinti S;Shulman GI;Seale P;Spiegelman BM
通讯作者：
Spiegelman BM
DOI：
10.1152/ajpendo.00330.2013
发表时间：
2014-03-01
影响因子：
5.1
作者：
Keipert, Susanne;Ost, Mario;Klaus, Susanne
通讯作者：
Klaus, Susanne