Maternal adipocyte connexin43 gap junctions affect breastmilk lactose levels and neonate growth in mice

Authors: HUANG, MINGYANG - Children'S Nutrition Research Center (CNRC); SONG, ANYING - City Of Hope Medical Center; CHEN, XI - Children'S Nutrition Research Center (CNRC); ISHTIAQ, SARAH - Children'S Nutrition Research Center (CNRC); WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC); HADSELL, DARRYL - Children'S Nutrition Research Center (CNRC); WANG, QIONG - City Of Hope Medical Center; ZHU, YI - Children'S Nutrition Research Center (CNRC)

Submitted to: Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/4/2022
Publication Date: 7/7/2022
Citation: Huang, M., Song, A., Chen, X., Ishtiaq, S., Wang, C., Hadsell, D.L., Wang, Q.A., Zhu, Y. 2022. Maternal adipocyte connexin43 gap junctions affect breastmilk lactose levels and neonate growth in mice. Biology. 11(7). Article 1023. https://doi.org/10.3390/biology11071023.
DOI: https://doi.org/10.3390/biology11071023

Interpretive Summary: It is unknown how adipocyte remodeling and communication between them contribute to breast milk production and breastmilk content. This study used a mouse model that lacked Connexin43, a protein responsible for cell-to-cell communication, in the adipocytes. It showed that the female mice had impaired breastmilk macronutrient component - lactose. Consequently, the pups they breastfeed gain less body weight. Our study suggests a critical role of adipocyte cell-to-cell communication in breast milk production.

Technical Abstract: 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.