Propensity to endoplasmic reticulum stress in deer mouse fibroblasts predicts skin inflammation and body weight gain.

ABSTRACT: The unfolded protein response (UPR) is involved in the pathogenesis of metabolic disorders, yet whether variations in the UPR among individuals influence the propensity for metabolic disease remains unexplored. Using outbred deer mice as a model, we show that the intensity of UPR in fibroblasts isolated early in life predicts the extent of body weight gain after high-fat diet (HFD) administration. Contrary to those with intense UPR, animals with moderate UPR in fibroblasts and therefore displaying compromised stress resolution did not gain body weight but developed inflammation, especially in the skin, after HFD administration. Fibroblasts emerged as potent modifiers of this differential responsiveness to HFD, as indicated by the comparison of the UPR profiles of fibroblasts responding to

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC8543066 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature