Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels and Neonate Growth in Mice.
Maternal Adipocyte Connexin43 Gap Junctions Affect Breastmilk Lactose Levels and Neonate Growth in Mice.
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DOI：
10.3390/biology11071023
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发表时间：
2022-07-07
期刊：
影响因子：
4.2
通讯作者：
Zhu, Yi
中科院分区：
文献类型：
--
作者：
Huang, Mingyang;Song, Anying;Chen, Xi;Ishtiaq, Sarah;Wang, Chunmei;Hadsell, Darryl L.;Wang, Qiong A.;Zhu, Yi
母乳喂养对母亲和婴儿都有许多健康益处。然而，营养过剩和美国肥胖症的稳步增加使许多母亲更难生产和表达母乳。此外，肥胖母亲的母乳质量经常受到影响，因为它含有更少的营养成分和更多的炎症成分。在这项研究中，我们使用小鼠来模拟这种现象。我们发现，繁殖开始时的短期高脂肪喂养会减少窝产仔数和幼崽体重。它还损害哺乳期间脂肪细胞的重塑。连接蛋白43是脂肪组织中间隙连接的主要结构单元。据推测，它在脂肪组织重塑中发挥重要作用，以适应乳腺发育和母乳生产。使用脂肪细胞中没有连接蛋白43的基因工程小鼠，我们证明了脂肪细胞连接蛋白43的缺失会影响哺乳期间脂肪细胞的消失，并影响乳汁成分，这被认为会损害幼崽的生长。总之，这项研究表明，增加或增强脂肪细胞连接蛋白43间隙连接可能有助于肥胖母亲产生更好的母乳，以支持他们的新生儿。母乳喂养为婴儿提供了广泛的健康益处。然而，营养过剩和美国产妇肥胖症的稳步增加使许多母亲更难生产和表达母乳，肥胖母亲的乳汁质量也经常受到影响。脂肪细胞是非哺乳期乳腺中的主要细胞类型，在哺乳期小鼠中表现出剧烈的形态和功能变化。充满脂质的脂肪细胞进行脂解，脂滴消失，为母乳生产提供脂肪酸和能量。一旦动物停止泌乳，这些脂质耗尽的脂肪细胞就会恢复为载脂细胞。这种组织的动态重塑可能是活跃的细胞间通讯的结果。缝隙连接蛋白43（Cx43）是乳腺脂肪组织中含量最丰富的连接蛋白，它构成了细胞间直接通讯的差距连接。它的表达在哺乳期增加，在肥胖的乳腺脂肪组织中减少，这是抵抗哺乳诱导的重塑。然而，Cx43是否是脂肪细胞重塑和母乳生产所必需的，以支持新生儿的生长尚未确定。在这项研究中，我们使用强力霉素诱导的脂肪细胞特异性Cx43缺失小鼠，并证明脂肪细胞Cx43在决定母乳中的碳水化合物水平方面发挥着至关重要的作用，这可能会影响新生儿的生长。
Breastfeeding offers many health benefits for both mothers and infants. However, overnutrition and a steady increase in obesity in the U.S. has made it harder for many mothers to produce and express breastmilk. Moreover, the quality of breastmilk from obese mothers is frequently compromised in that it contains fewer nutrients and more inflammatory components. In this study, we used mice to model this phenomenon. We found that short-term high-fat feeding at the start of breeding reduces litter size and pups’ body weight. It also impairs adipocyte remodeling during lactation. Connexin43 is the primary building block for gap junctions in the adipose tissue. It is postulated to play an essential role in adipose tissue remodeling to accommodate mammary gland development and breastmilk production. Using genetically engineered mice without Connexin43 in their adipocytes, we demonstrated that the deletion of adipocyte Connexin43 affects the disappearance of adipocytes during lactation and affects milk composition, which is postulated to impair the pups’ growth. Altogether, this study suggests that increasing or enhancing adipocyte Connexin43 gap junctions may help obese mothers produce better breastmilk to support their neonates. Breastfeeding offers a broad spectrum of health benefits for infants. However, overnutrition and a steady increase in maternal obesity in the U.S. have made it harder for many mothers to produce and express breastmilk, and the quality of milk from obese mothers is also frequently compromised. Adipocytes, the primary cell type in the non-lactating breast, display a drastic morphological and functional change during lactation in mice. Lipid-filled adipocytes undergo lipolysis, and lipid droplets disappear to provide fatty acids and energy for breastmilk production. Once the animal stops lactation, these lipid-depleted adipocytes return as lipid-laden cells. This dynamic remodeling of the tissue is likely the result of active intercellular communications. Connexin43 (Cx43) is the most abundant connexin in the mammary adipose tissue that makes up the gap junctions for direct intercellular communications. Its expression is increased during lactation and reduced in obese mammary adipose tissue, which is resistant to lactation-induced remodeling. However, whether Cx43 is required for adipocyte remodeling and breastmilk production to support neonates’ growth has not been established. In this study, we used doxycycline-inducible adipocyte-specific Cx43-deleted mice and demonstrated that adipocyte Cx43 played a vital role in determining the carbohydrate levels in breastmilk, which may subsequently affect neonates’ growth.
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