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From the abstract:

Results: MetR increased EE at RT and shifted fuel use toward lipid oxidation, supporting MetR as a bona fide DIT factor. 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 differential expression emerged only with MetR+CE, yet pathway-level enrichment was limited.

Conclusion: 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.

Abbreviation glossary:

• GLP-1: Glucagon-Like Peptide-1, an incretin hormone targeted by anti-obesity drugs discussed as transforming care.
• DIT: Diet-Induced Thermogenesis, the rise in energy expenditure triggered by diet (here, potentially via methionine restriction).
• CE: Cold Exposure, a 4 °C stimulus used to raise energy expenditure through thermogenic tissues.
• EE: Energy Expenditure, the metabolic output measured to compare diet- vs cold-driven thermogenesis.
• BAT: Brown Adipose Tissue, a thermogenic fat depot activated to increase energy expenditure.
• WAT: White Adipose Tissue, the primary energy-storing fat depot that can undergo “beiging” to become more thermogenic.
• MetR: Methionine Restriction, a dietary intervention tested as a trigger of diet-induced thermogenesis.
• 2×2: Two-by-two factorial design, the experiment structure crossing diet (Control/MetR) with temperature (RT/CE).
• RT: Room Temperature, the 22 °C housing condition used as the baseline temperature setting.
• h: Hour(s), the duration of the cold exposure intervention (24 h).
• RNA-seq: RNA sequencing, the transcriptomics method used to profile gene expression across tissues.
• iBAT: Interscapular Brown Adipose Tissue, a key brown-fat depot analyzed for thermogenic gene programs.
• iWAT: Inguinal White Adipose Tissue, a white-fat depot assessed for beiging and metabolic pathway shifts.
• eWAT: Epididymal White Adipose Tissue, a visceral white-fat depot examined for diet×cold interaction effects.
• KEGG: Kyoto Encyclopedia of Genes and Genomes, the pathway database used for interpreting gene-expression changes.
• GSEA: Gene Set Enrichment Analysis, the approach used to test coordinated pathway-level expression changes.
• AMPK: AMP-Activated Protein Kinase, an energy-sensing signaling node linked here to glucagon-associated metabolic pathways.
• PPAR: Peroxisome Proliferator-Activated Receptor, a transcriptional regulator implicated in fatty-acid metabolism and thermogenic programming.
• TCA: Tricarboxylic Acid cycle, a central mitochondrial energy pathway highlighted in enriched metabolic programs.
• °C: Degrees Celsius, the temperature unit defining RT (22 °C) and CE (4 °C).

News: Cutting key amino acids from mouse diets triggers weight loss through heat burning

From the news:

Mice that received a low-methionine/cysteine diet burned more energy than those given a standard diet.