Huang Mingyang, Song Anying, Chen Xi, Ishtiaq Sarah, Wang Chunmei, Hadsell Darryl L, Wang Qiong A, Zhu Yi
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular Endocrinology, Diabetes and Metabolism Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Biology (Basel). 2022 Jul 7;11(7):1023. doi: 10.3390/biology11071023.
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.
母乳喂养对婴儿有广泛的健康益处。然而，美国的营养过剩以及孕产妇肥胖率的持续上升，使得许多母亲更难分泌和挤出母乳，而且肥胖母亲所产母乳的质量也常常受到影响。脂肪细胞是未哺乳乳房中的主要细胞类型，在小鼠哺乳期会发生剧烈的形态和功能变化。充满脂质的脂肪细胞会进行脂肪分解，脂滴消失，为母乳生产提供脂肪酸和能量。一旦动物停止哺乳，这些脂质消耗殆尽的脂肪细胞又会变回充满脂质的细胞。组织的这种动态重塑可能是活跃的细胞间通讯的结果。连接蛋白43（Cx43）是乳腺脂肪组织中最丰富的连接蛋白，它构成了细胞间直接通讯的间隙连接。其在哺乳期会增加，而在对泌乳诱导重塑有抗性的肥胖乳腺脂肪组织中会减少。然而，Cx43是否是脂肪细胞重塑和母乳生产以支持新生儿生长所必需的尚未明确。在本研究中，我们使用了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起着至关重要的作用，这可能随后会影响新生儿的生长。
