Whole transcriptome analysis and validation of metabolic pathways in subcutaneous adipose tissues during FGF21-induced weight loss in non-human primates

Sara A. Murray, Louise S. Dalbøge, Karalee Baquero, Christina A. Sanford, Ayesha Misquith, Aaron J. Mercer, Thomas H. Meek, Mette Guldbrandt, Birgitte Andersen, Paul Kievit, Kevin Grove, Burak Kutlu

    Research output: Contribution to journalArticlepeer-review

    5 Scopus citations

    Abstract

    Fibroblast growth factor 21 (FGF21) induces weight loss in mouse, monkey, and human studies. In mice, FGF21 is thought to cause weight loss by stimulating thermogenesis, but whether FGF21 increases energy expenditure (EE) in primates is unclear. Here, we explore the transcriptional response and gene networks active in adipose tissue of rhesus macaques following FGF21-induced weight loss. Genes related to thermogenesis responded inconsistently to FGF21 treatment and weight loss. However, expression of gene modules involved in triglyceride (TG) synthesis and adipogenesis decreased, and this was associated with greater weight loss. Conversely, expression of innate immune cell markers was increased post-treatment and was associated with greater weight loss. A lipogenesis gene module associated with weight loss was evaluated by testing the function of member genes in mice. Overexpression of NRG4 reduced weight gain in diet-induced obese mice, while overexpression of ANGPTL8 resulted in elevated TG levels in lean mice. These observations provide evidence for a shifting balance of lipid storage and metabolism due to FGF21-induced weight loss in the non-human primate model, and do not fully recapitulate increased EE seen in rodent and in vitro studies. These discrepancies may reflect inter-species differences or complex interplay of FGF21 activity and counter-regulatory mechanisms.

    Original languageEnglish (US)
    Article number7287
    JournalScientific Reports
    Volume10
    Issue number1
    DOIs
    StatePublished - Dec 1 2020

    ASJC Scopus subject areas

    • General

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