Evidence map›Paper›PMID 41842927›Full record

ArticleeLife2026

Dietary sulfur amino acid restriction elicits a cold-like transcriptional response in inguinal but not epididymal white adipose tissue of male mice.

Philip M M Ruppert, Aylin S Gueller, Marcus Skjæveland, Natasa Stanic, Jan-Wilhelm Kornfeld

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Philip M M RuppertFunctional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0000-0002-4028-8200
Aylin S GuellerFunctional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0009-0000-3636-2773
Marcus SkjævelandFunctional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0009-0009-7393-4721
Natasa StanicFunctional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Jan-Wilhelm KornfeldFunctional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID https://orcid.org/0000-0002-6802-4442

Funding

European Molecular Biology Organization ALTF 676-2021Novo Nordisk Fonden NNF21OC0070263
6 · The paper itself

Abstract

About 1 billion people are living with obesity worldwide. GLP-1-based drugs have massively transformed care, but long-term consequences are unclear in part due to reductions in energy expenditure with ongoing use. Diet-induced thermogenesis (DIT) and cold exposure (CE) raise EE via brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT). Methionine restriction (MetR) is a candidate DIT stimulus, but its EE effect has not been benchmarked against CE, nor have their tissue-level interactions been defined. In a 2×2 design (Control vs. MetR; room temperature, RT: 22°C vs. CE: 4°C for 24 hr), we used male C57BL/6 N mice to benchmark MetR-induced thermogenesis against CE and mapped how diet and temperature interact across tissues. Bulk RNA-seq profiled liver, iBAT, iWAT, and eWAT. Differential expression was modeled with main effects and a diet × temperature interaction. KEGG GSEA was used to assess pathway-level enrichment. MetR increased EE at RT and shifted fuel use towards lipid oxidation, supporting MetR as a bona fide DIT stimulus. CE elevated EE across diets and blunted diet differences. Transcriptomic responses were tissue-specific: in liver, CE dominated gene induction while MetR and CE cooperatively repressed genes. The combination enriched glucagon/AMPK-linked and core metabolic pathways. In iBAT, CE dominated thermogenic and lipid-oxidation programs with minimal MetR contribution. In iWAT, MetR and CE acted largely additively with high concordance, enhancing fatty-acid degradation, PPAR signaling, thermogenesis, and TCA cycle pathways. In eWAT, robust co-dependent and synergistic differential expression emerged only with MetR+CE. MetR is a genuine DIT stimulus that remodels metabolism in a tissue-specific manner. Our study provides a tissue-resolved transcriptomic resource that benchmarks diet-induced (MetR) against cold-induced thermogenesis and maps their interactions across liver, iBAT, iWAT, and eWAT.

Indexed as

Adipose Tissue, WhiteCold TemperatureDietMethionineThermogenesisAnimalsEpididymisMaleMiceMice, Inbred C57BLMethionineadipose tissuebiochemistrychemical biologychromosomescold exposuredietary methionine restrictionenergy metabolismgene expressionmousetranscriptomics

Identifiers

PMID41842927
PMCPMC12995289

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.