GEO series

Overnutrition directly impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations

GSE294396 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/02/05 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 16 samples: 16 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Overnutrition in mice impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptationsThe Journal of clinical investigation · 2026

Summary (written by the submitters)

Thyroid hormones (THs: T3 and T4) are key regulators of metabolic rate and nutrient metabolism. They are controlled centrally and peripherally in a coordinated manner to elegantly match T3-mediated energy expenditure (EE) to energy availability. Hypothyroidism reduces EE and has long been blamed for obesity; however, emerging evidence suggests that, instead, obesity may drive thyroid dysfunction.

Read the full summary ↓

Thus, we used a mouse model of diet-induced obesity to determine its direct effects on thyroid histopathology and function, deiodinase activity, and T3 action. Strikingly, overnutrition induced hypothyroidism within 3 weeks. Levels of thyroidal THs and the TH precursor protein thyroglobulin decreased, and ER stress was induced, indicating that thyroid function was directly impaired. We also observed pronounced morphological and vascular expansion in the thyroid. Overnutrition additionally suppressed T4 activation, rendering the mice resistant to T4 and reducing EE. Our findings collectively show that overnutrition deals a double strike to TH biosynthesis and action, despite large efforts to adapt—but, fortunately, thyroid dysfunction in mice can be reversed by weight loss. In humans, BMI correlated with thyroidal vascularization, importantly signaling initial translatability. These studies lay the groundwork for novel obesity therapies that tackle hypothyroidism—which are much-needed, as no current obesity treatment works for everyone.

Published in

Overnutrition in mice impairs thyroid hormone biosynthesis and utilization, causing hypothyroidism, despite remarkable thyroidal adaptations

Rampy J, Torres-Manzo AP, Hoffsmith K et al. · The Journal of clinical investigation 2026 · PMID 41983397 · doi:10.1172/JCI194207

This dataset

Open GSE294396 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE294396_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1249381 and SRA study SRP577854. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41983397) ↗

Study design

16 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 16 sample titles: 16 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8903862 WT, M22, CD, 6W
GSM8903863 WT, M43, CD, 6W
GSM8903864 WT, M45, CD, 6W
GSM8903865 WT, M48, CD, 6W
GSM8903866 WT, M5, HF+SD, 6W
GSM8903867 WT, M18, HF+SD, 6W
GSM8903868 WT, M34, HF+SD, 6W
GSM8903869 WT, M35, HF+SD, 6W
GSM8903870 WT, M53, CD, 3W
GSM8903871 WT, M54, CD, 3W
GSM8903872 WT, M55, CD, 3W
GSM8903873 WT, M96, CD, 3W
GSM8903874 WT, M7, HF+SD, 3W
GSM8903875 WT, M19y, HF+SD, 3W
GSM8903876 WT, M20y, HF+SD, 3W
GSM8903877 WT, M31, HF+SD, 3W

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.