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Updated: Dec 31, 2025
Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
Published on: September 9, 2021
Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice
1Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, China.
Objective:
Long-term glucocorticoids (GCs) therapy usually causes many metabolic side effects, including fatty liver. However, the molecular mechanisms remain poorly understood. Herein, we explored the molecular basis of GCs in the development of fatty liver.
Methods:
C57BL/6 male mice were injected with Dexamethasone (DEX) while mouse primary hepatocytes (MPHs), HepG2 and Hep1-6 cells were cultured in the presence of DEX. Genes expression in liver tissues and hepatocytes were assessed by quantitative real-time PCR and western blotting, respectively. To explore whether Periostin is involved in the development of GCs-induced fatty liver, wild-type and Periostin knockout mice were treated with DEX or vehicle control. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the regulatory roles of GCs on Periostin expression.
Results:
We show that treatment of dexamethasone (DEX), a synthetic analog of GCs, led to the accumulation of triglycerides in the livers of mice, but not in cultured hepatocytes, suggesting that GCs may promote liver steatosis through integrative organ crosstalk mediated by systemic factors. We further found that DEX upregulated the expression levels of Periostin in white adipose tissues, which in turn promoted liver steatosis. Administration of a Periostin-neutralizing antibody or genetic ablation of Periostin largely attenuated DEX-induced hepatic steatosis in mice.
Conclusions:
Our findings provided a novel insight that GCs could promote liver steatosis through integrative organ crosstalk mediated by white fat-secreted Periostin. These results establish Periostin as an endocrine factor with therapeutic potential for the treatment of GCs-associated fatty liver.
Insights
Long-term glucocorticoid (GC) therapy can cause fatty liver. This study reveals that GCs promote liver steatosis via white adipose tissue-secreted Periostin, offering a potential therapeutic target.
Area of Science:
- Endocrinology
- Metabolic Syndrome
- Molecular Biology
Background:
- Long-term glucocorticoid (GC) therapy is associated with metabolic side effects, notably fatty liver.
- The precise molecular mechanisms underlying GC-induced hepatic steatosis remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which GCs contribute to the development of fatty liver.
- To investigate the role of Periostin in GC-induced hepatic steatosis.
Main Methods:
- Dexamethasone (DEX) administration in mice and cell culture models (primary mouse hepatocytes, HepG2, Hep1-6).
- Gene expression analysis using quantitative real-time PCR and Western blotting.
- Studies involving wild-type and Periostin knockout mice, Periostin-neutralizing antibodies, luciferase reporter assays, and chromatin immunoprecipitation assays.
Main Results:
- DEX treatment induced triglyceride accumulation in mouse livers but not in isolated hepatocytes, suggesting systemic factors are involved.
- DEX upregulated Periostin expression in white adipose tissue, which promoted liver steatosis.
- Periostin neutralization or genetic ablation significantly reduced DEX-induced hepatic steatosis.
Conclusions:
- Glucocorticoids promote liver steatosis through an endocrine mechanism involving white fat-secreted Periostin.
- Periostin emerges as a key mediator in GC-associated fatty liver and a potential therapeutic target.
