Oncostatin M promotes lipolysis in white adipocytes
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Updated: Sep 24, 2025

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
Pim P van Krieken1,2, Julian Roos3, Pamela Fischer-Posovszky3
1Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Zurich, Zurich, Switzerland.
Abstract:
Oncostatin M (OSM) is a member of the glycoprotein 130 cytokine family that is involved in chronic inflammation and increased in adipose tissue under obesity and insulin resistance. OSM was shown to inhibit adipogenesis, suppress browning, and contribute to insulin resistance in cultured white adipocytes. In contrast, OSM may have a metabolically favourable role on adipocytes in mouse models of obesity and insulin resistance. However, a putative role of OSM in modulating lipolysis has not been investigated in detail to date. To address this, cultured white adipocytes of mouse or human origin were exposed to 10 or 100 ng/ml of OSM for various time periods. In murine 3T3-L1 cells, OSM stimulation directly activated hormone-sensitive lipase (HSL) and other players of the lipolytic machinery, and dose-dependently increased free fatty acid and glycerol release. In parallel, OSM attenuated insulin-mediated suppression of lipolysis and induced phosphorylation of serine-residues on the insulin receptor substrate-1 (IRS1) protein. Key experiments were verified in a second murine and a human adipocyte cell line. Inhibiton of extracellular signal-regulated kinase (ERK)-1/2 activation, abolished OSM-mediated HSL phosphorylation and lipolysis. In conclusion, OSM signalling directly promotes lipolysis in white adipocytes in an ERK1/2-dependent manner.
Insights
Oncostatin M (OSM) directly promotes lipolysis in white adipocytes by activating hormone-sensitive lipase (HSL) via ERK1/2 signaling. This finding clarifies OSM's complex role in metabolic regulation and insulin resistance.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Oncostatin M (OSM), a glycoprotein 130 cytokine, is implicated in chronic inflammation and metabolic dysfunction.
- OSM's role in adipocytes is complex, with inhibitory effects on adipogenesis and browning, yet potentially favorable roles in obesity models.
Purpose of the Study:
- To investigate the role of Oncostatin M (OSM) in modulating lipolysis in white adipocytes.
- To elucidate the molecular mechanisms underlying OSM-induced lipolysis.
Main Methods:
- Primary and cell line-derived white adipocytes (murine and human) were treated with OSM.
- Assays included measurement of lipolysis markers (free fatty acids, glycerol), hormone-sensitive lipase (HSL) activity, and protein phosphorylation (IRS1, ERK1/2).
- Specific inhibitors of extracellular signal-regulated kinase (ERK)-1/2 were used to assess pathway involvement.
Main Results:
- OSM stimulation directly activated hormone-sensitive lipase (HSL) and increased lipolysis in a dose-dependent manner.
- OSM attenuated insulin's suppressive effect on lipolysis and induced insulin receptor substrate-1 (IRS1) phosphorylation.
- Inhibition of ERK1/2 activation abolished OSM-mediated HSL phosphorylation and lipolysis.
Conclusions:
- Oncostatin M signaling directly promotes lipolysis in white adipocytes.
- This effect is mediated through the extracellular signal-regulated kinase (ERK)-1/2 pathway.
- OSM's pro-lipolytic action contributes to its complex role in metabolic regulation and insulin resistance.
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