GEO series
Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation
GSE342640
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
159 samples
Submitted 2026/08/07
Platform GPL24247Platform GPL24676
Summary
Insulin resistance (IR) has emerged as a risk factor for lactation insufficiency and delays the onset of milk secretion after childbirth, termed secretory activation (SA). This may cause inadequate infant weight gain and early breastfeeding cessation. However, the mechanisms underlying delayed SA in insulin resistant women are unknown. To investigate this, we characterized the mammary transcriptomes and IR-related hormones of 75 breastfeeding women with healthy term infants during postpartum days 1-5. Participants were divided into IR tertiles based on plasma leptin-to-adiponectin ratio measurements. Those in the highest tertile had later SA onset with greater neonatal weight loss during postpartum days 1-5. Transcriptomic analysis on postpartum day 2 (n=4 high IR vs. n=8 low IR participants) showed transient suppression of mammary insulin and prolactin signaling genes, increased pro-inflammatory gene expression and altered expression of >200 mammary mitochondrial genes. These alterations were absent on postpartum days 3-5. Cultured mammary epithelial cells (MECs) treated with insulin showed upregulation of prolactin signaling and oxidative phosphorylation (OXPHOS) genes, with imaging and bioenergetic studies demonstrating that insulin promotes mitochondrial biogenesis and OXPHOS. Thus, our findings delineate roles for insulin in mammary bioenergetics and highlight mitochondrial dysfunction as a mechanism for delayed SA in insulin resistant women.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE342640_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 159 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1508691 and SRA study SRP724715. Searching any of these in the dataset finder brings you back here.
Study design
9 conditions, mostly with about 5 replicates each
HC11 cells_8h control_biol ×5
HC11 cells_8h 100nM insulin_biol ×5
WT 0nM insulin control, biol ×5
Akt knockdown, 0nM insulin, biol ×5
10nM insulin, 4h, biol ×5
10nM insulin, 8h, biol ×5
100nM insulin, 1h, biol ×5
10nM insulin, 1h, biol ×3
+1 more
Supports a case/control comparison: 5 samples read as cases, 10 as controls.
9 replicated groups read from the first 40 of 159 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9935071 HC11 cells_8h control_biol rep 1
- GSM9935072 HC11 cells_8h control_biol rep 2
- GSM9935073 HC11 cells_8h control_biol rep 3
- GSM9935074 HC11 cells_8h control_biol rep 4
- GSM9935075 HC11 cells_8h control_biol rep 5
- GSM9935076 HC11 cells_8h 100nM insulin_biol rep 1
- GSM9935077 HC11 cells_8h 100nM insulin_biol rep 2
- GSM9935078 HC11 cells_8h 100nM insulin_biol rep 3
- GSM9935079 HC11 cells_8h 100nM insulin_biol rep 4
- GSM9935080 HC11 cells_8h 100nM insulin_biol rep 5
- GSM9935081 WT 0nM insulin control, biol rep 1
- GSM9935082 WT 0nM insulin control, biol rep 2
- GSM9935083 WT 0nM insulin control, biol rep 3
- GSM9935084 WT 0nM insulin control, biol rep 4
- GSM9935085 WT 0nM insulin control, biol rep 5
- GSM9935086 Akt knockdown, 0nM insulin, biol rep 1
- GSM9935087 Akt knockdown, 0nM insulin, biol rep 2
- GSM9935088 Akt knockdown, 0nM insulin, biol rep 3
- GSM9935089 Akt knockdown, 0nM insulin, biol rep 4
- GSM9935090 Akt knockdown, 0nM insulin, biol rep 5
- GSM9935091 10nM insulin, 1h, biol rep 1
- GSM9935092 10nM insulin, 1h, biol rep 2
- GSM9935093 10nM insulin, 1h, biol rep 3
- GSM9935094 10nM insulin, 4h, biol rep 1
- GSM9935095 10nM insulin, 4h, biol rep 2
- GSM9935096 10nM insulin, 4h, biol rep 3
- GSM9935097 10nM insulin, 4h, biol rep 4
- GSM9935098 10nM insulin, 4h, biol rep 5
- GSM9935099 10nM insulin, 8h, biol rep 1
- GSM9935100 10nM insulin, 8h, biol rep 2
- GSM9935101 10nM insulin, 8h, biol rep 3
- GSM9935102 10nM insulin, 8h, biol rep 4
- GSM9935103 10nM insulin, 8h, biol rep 5
- GSM9935104 100nM insulin, 1h, biol rep 1
- GSM9935105 100nM insulin, 1h, biol rep 2
- GSM9935106 100nM insulin, 1h, biol rep 3
- GSM9935107 100nM insulin, 1h, biol rep 4
- GSM9935108 100nM insulin, 1h, biol rep 5
- GSM9935109 100nM insulin, 4h, biol rep 1
- GSM9935110 100nM insulin, 4h, biol rep 2
+ 119 more — browse all 159 samples with per-sample file links →
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