biostudies-arrayexpressTania Quesada-LópezMus musculusHISAT2Illuminahttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-15994Tirzepatide is an anti-obesity drug based on dual agonism of the incretin receptors GLP-1R and GIPR. Its anti-obesity effect is largely based on its action of reducing food intake. However, there are suggestive indications that tirzeparide may exert effects on adipose tissues beyond those resulting from fat loss due to reduced intake. To investigate this, we treated mice that had previously been made obese through a high-fat diet with tirzepatide. Tzp group experienced a reduction in body weight. Glucose tolerance improved in tirzepatide-treated obese mice, independently of reduced food intake. Tirzepatide treatment also lowered the inflammatory status of obese mice, an effect that, in this case, was attributable to decreased food consumption. Tirzepatide exerted distinct effects on brown adipose tissue relative to white adipose tissues, significantly boosting thermogenic activity and modifying its gene expression pattern, including the upregulation of genes linked to thermogenesis and substrate oxidation. White adipose tissues responded differently, being primarily affected in their lipid metabolism. These effects were specific to tirzepatide treatment and not attributable to reduced food intake. Our results indicate that tirzepatide affects the function and metabolism of adipose tissues and especially induces activation of brown adipose tissue in mice, which may be relevant for future human studies to ascertain the mechanisms of tirzepatide metabolic benefits.biostudies-arrayexpressNucleic Acid Extraction - Total RNA was extracted using a NucleoSpin RNA kit, 2ug of total RNA was used for the construction of seq librariesSequencing - Adaptor ligation, purification of 100 base-pair cDNA fragments, amplification of these fragments, and library preparation were performed according to the manufacturer’s instructions (Illumina) and sequenced using Illumina NovaSeq X-25B (PE150).Library Construction - Integrity of RNA samples was determined using Qubit RNA IQ Assay (Invitrogen). A purification of 2ug from the obtained mRNA was performed using TruSeq RNA sample prep kit v2 (Illumina). Adaptor ligation, purification of 100 base-pair cDNA fragments, amplification of these fragments, and library preparation were performed according to the manufacturer’s instructions (Illumina) and sequencedSample Collection - Mice were housed at 22 °C under a 12-h light cycle (lights on, from 08.00 am to 08.00 pm) with 50% ±5% relative humidity with free access to water and a standard diet.  Mice were fed a high-fat diet for 15 weeks (#D12451, 45% Kcal fat, Envigo). Following the 15-weeks HFD period, obese mice received treatment with TZP (Mounjaro Lilly, Madrid Spain). TZP was administered via daily intraperitoneal (i.p.) injections at a dose of 10 mg/kg for 5 days, followed by 20 mg/kg for an additional 7 days. Control mice received saline injections.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesSequence Alignment - The sequenced 150-base pair paired-end reads were quality-checked using FastQC, and Quality control alignment. The obtained reads were subsequently aligned to the mouse reference genome (GRCm39) using HISAT2 (Mortazavi et al., 2008) uses a graph-based alignment and has succeeded HISAT and TOPHAT2.Data Transformation - Description. Fragments Per Kilobase of transcript per Million mapped reads (FPKM) is a simple expression level normalization method. The FPKM normalizes read count based on gene length and the total number of mapped reads.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq XRNA-seq of coding RNAMus musculusTania Quesada-LópezMarta GiraltAnna PlanavilaFrancesc VillarroyaMarion PeyrouAlbert Blasco-RosetAlbert Mestres-ArenasfalseDifferential Effects Of The Anti-Obesity Drug Tirzepatide On Adipose Tissues: Brown Fat As A Key TargetTirzepatide is an anti-obesity drug based on dual agonism of the incretin receptors GLP-1R and GIPR. Its anti-obesity effect is largely based on its action of reducing food intake. However, there are suggestive indications that tirzeparide may exert effects on adipose tissues beyond those resulting from fat loss due to reduced intake. To investigate this, we treated mice that had previously been made obese through a high-fat diet with tirzepatide. Tzp group experienced a reduction in body weight. Glucose tolerance improved in tirzepatide-treated obese mice, independently of reduced food intake. Tirzepatide treatment also lowered the inflammatory status of obese mice, an effect that, in this case, was attributable to decreased food consumption. Tirzepatide exerted distinct effects on brown adipose tissue relative to white adipose tissues, significantly boosting thermogenic activity and modifying its gene expression pattern, including the upregulation of genes linked to thermogenesis and substrate oxidation. White adipose tissues responded differently, being primarily affected in their lipid metabolism. These effects were specific to tirzepatide treatment and not attributable to reduced food intake. Our results indicate that tirzepatide affects the function and metabolism of adipose tissues and especially induces activation of brown adipose tissue in mice, which may be relevant for future human studies to ascertain the mechanisms of tirzepatide metabolic benefits.2026-02-16T00:00:00Z2026-05-27T17:52:18.756Z2025-11-13T14:32:10.995ZE-MTAB-15994ERP183713EFO_0002944EFO_0004170EFO_0004917EFO_0005518EFO_0003816EFO_0003738EFO_0004184