Insulin sensitivity and mitochondrial homeostasis connect lactation to maternal metabolic health
Laura L. Hernandez
Laura L. Hernandez
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Commentary

Insulin sensitivity and mitochondrial homeostasis connect lactation to maternal metabolic health

Abstract

Lactation insufficiency in postpartum women has been associated with obesity and insulin resistance, among other risk factors. Challenges related to translating findings from animal models of lactation and the limited ability to study pregnant and lactating women in clinical trials have impeded more detailed mechanistic understanding of this relationship. In this issue of the JCI, Meng et al. combined studies in human milk samples and in vitro mammary epithelial cell models from humans and rodents to provide compelling evidence that mitochondrial dysfunction mediates the link between insulin resistance and lactation insufficiency. Notably, they observed that chronic exposure to high levels of insulin led to mitochondrial fragmentation and loss of volume in mouse mammary epithelial cells. This framework linking mitochondria, insulin signaling, and lactation should be extended to in vivo models and primary human tissues to better define the mechanisms supporting successful lactation.

Authors

Laura L. Hernandez

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Figure 1

Investigating the association between insulin resistance and insufficient glandular tissue and low milk supply.

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Investigating the association between insulin resistance and insufficien...
(A) Meng et al. (14) used RNA extraction of the milk fat globule to look at gene expression in mammary epithelial cells in pregnant women who were categorized as insulin resistant at 36 weeks’ gestation. Women with increased insulin resistance exhibited increased expression of pathways related to mitochondrial dysfunction compared with insulin-sensitive participants. (B) In human and mouse mammary epithelial cells, treatment with high concentrations of insulin increased AKT signaling. The authors also observed increases in oxidative phosphorylation, extracellular acidification, glycolytic capacity, and oxygen consumption consistent with disruptions in mitochondrial homeostasis as well as a reduction in mitochondrial volume and increased mitochondrial fragmentation. (C) Together, the findings indicate that mitochondrial dysfunction links insulin resistance to lactation insufficiency.