Skeletal Muscle DPT Ameliorates Obesity and Metabolic Dysfunction via the PERK/eIF2α/ATF4-GDF15 Axis.

Authors

Lingxin You, Bo Xu, Tingting Wen, Ying Chen, Lijun Yao, Zhuo Chen, Baocheng Wan, Fan Yang, Xiangtian Yu, Rong Zhang, Hong Zhang, Jing Yan, Cheng Hu

Published in

Diabetes. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

We identified dermatopontin (DPT) as a previously unrecognized compensatory regulator that is upregulated in skeletal muscle in obesity and preserves muscle function and systemic metabolic homeostasis, offering a potential therapeutic target for metabolic disorders. Mechanistically, DPT activates an adaptive PERK/eIF2α/ATF4 endoplasmic reticulum stress axis specifically under metabolic stress, but not under normal conditions, which enhances muscle function and directly counteracts metabolic deterioration, revealing a protective signaling cascade. This DPT-driven endoplasmic reticulum stress axis transcriptionally upregulates growth differentiation factor (GDF) 15 expression and secretion in muscle. Muscle-derived GDF15 exerts both local muscle-autonomous and systemic protective effects, uncovering a previously unrecognized muscle-to-organ cross-talk axis.

PMID:
42873616
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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