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Updated: Feb 13, 2026

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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Ufmylation-Deficient DDRGK1 Ameliorates Obesity by Inhibiting FASN-Mediated Adipocyte Lipogenesis

Yin Li1, Tangjun Zhou1, Xiao Yang1

  • 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 11, 2026
PubMed

Insights

Researchers discovered a new pathway involving DDRGK1 and UFMylation that stabilizes Fatty Acid Synthase (FASN). Targeting this axis offers a novel therapeutic strategy for obesity and metabolic dysfunction.

Area of Science:

  • Biochemistry
  • Metabolic Research
  • Obesity Studies

Background:

  • Fatty acid synthase (FASN) is key in obesity via de novo lipogenesis (DNL).
  • Its regulation by post-translational modifications, especially in obesity, is not fully understood.
  • While FASN protein is elevated in overweight individuals, FASN mRNA shows an inverse correlation with BMI.

Purpose of the Study:

  • To investigate the role of post-translational modifications in FASN regulation related to obesity.
  • To identify novel molecular targets for treating obesity-associated metabolic dysfunction.

Main Methods:

  • Clinical investigation of human adipose tissue (n=23).
  • Transcriptomic analysis of 770 GEO samples.
  • Genetic disruption using Ddrgk1K268R mutant mice.
  • Single-nucleus RNA sequencing of inguinal white adipose tissue (iWAT).
  • In vitro adipocyte studies and lipidomic profiling.

Main Results:

  • DDRGK1 identified as a UFMylation effector that stabilizes FASN by inhibiting ubiquitination.
  • Ddrgk1K268R mutant mice showed reduced body weight and fat mass under high-fat diet (HFD), with improved glucose homeostasis.
  • Mutant mice exhibited reprogrammed metabolic flux in iWAT and attenuated DNL.
  • DDRGK1 deficiency impaired adipocyte lipid droplet formation via FASN destabilization.

Conclusions:

  • The adipocyte-specific DDRGK1-UFMylation-FASN axis is a novel regulator of obesity.
  • This pathway represents a potential therapeutic target for obesity and related metabolic disorders.
Keywords:
DDRGK1FASNUFMylationde novo lipogenesis

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