2. Academic Validation
  3. Quercetin inhibits adipogenesis and promotes adipose tissue remodeling through lipophagy-mediated lipid droplet (LD) clearance

Quercetin inhibits adipogenesis and promotes adipose tissue remodeling through lipophagy-mediated lipid droplet (LD) clearance

  • Chem Biol Interact. 2026 Jun 1:432:112053. doi: 10.1016/j.cbi.2026.112053.
Zihan Chen 1,  Baoying Peng 2,  Lei Zhao 1,  Zhibiao Huang 2,  Meifen Chen 2,  Suisheng Zheng 2,  Yujia Jiang 2,  Liang Zhou 3,  Xin Li 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Center for Disease Control and Prevention, NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, No. 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province, 511430, PR China; School of Public Health, Southern Medical University, No. 1023 - 1063, Shatai South Road, Baiyun District, Guangzhou, Guangdong Province, 510515, PR China.
  • 2 Guangdong Provincial Center for Disease Control and Prevention, NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, No. 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province, 511430, PR China.
  • 3 School of Public Health, Southern Medical University, No. 1023 - 1063, Shatai South Road, Baiyun District, Guangzhou, Guangdong Province, 510515, PR China.
  • 4 Guangdong Provincial Center for Disease Control and Prevention, NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, No. 160 Qunxian Road, Dashi, Panyu District, Guangzhou, Guangdong Province, 511430, PR China. Electronic address: [email protected].
PMID: 41864473 DOI: 10.1016/j.cbi.2026.112053
Abstract

Quercetin, a dietary flavonoid, has been implicated in obesity prevention; however, its role in adipocyte differentiation and adipose tissue remodeling remains incompletely defined. In HFD-fed C57BL/6 mice, quercetin dose-dependently attenuated body weight gain and reduced white adipose tissue expansion without altering food intake. Histological analysis revealed decreased adipocyte hypertrophy and improved adipose tissue architecture, indicating enhanced tissue remodeling. In differentiating 3T3-L1 adipocytes, quercetin markedly suppressed lipid droplet accumulation during the early stage of adipogenesis and enhanced autophagic flux, as evidenced by increased LC3-II conversion, p62 degradation, and autolysosome formation. Mechanistically, quercetin activated the AMPK-DAPK3-ULK1 signaling axis, promoting lipophagy and limiting LD formation during adipocyte differentiation. Proteomic analysis demonstrated cell-type-specific regulation: DAPK1 predominated in whole adipose tissue under metabolic stress, whereas DAPK3 was selectively upregulated in metabolically active differentiating adipocytes, aligning with its role in promoting lipophagy. Collectively, these findings demonstrate that quercetin suppresses adipocyte differentiation and promotes adipose tissue remodeling through DAPK3-mediated lipophagy, identifying DAPK3 as a key regulatory factor in adipogenesis.

Keywords

AMPK; Adipogenesis; Autophagy; DAPK; Lipid droplet (LD); Lipophagy; Obesity; Quercetin.

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