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Published on: March 17, 2023
Negative regulation of adipose-expressed galectin-12 by isoproterenol, tumor necrosis factor alpha, insulin and
Mathias Fasshauer1, Johannes Klein, Ulrike Lossner
1Department of Internal Medicine III, University of Leipzig, Leipzig 04103, Germany.
Objective:
Galectin-12 has recently been shown to be a predominantly adipocyte-expressed protein which is stimulated by insulin-sensitizing thiazolidinediones and possesses apoptosis-inducing activity.
Methods:
To further clarify galectin-12 regulation and its potential involvement in the development of insulin resistance, 3T3-L1 adipocytes were chronically treated with various hormones known to impair insulin sensitivity, and galectin-12 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction.
Results:
Treatment of 3T3-L1 cells for 16 h with 10 micromol/l isoproterenol, 100 nmol/l insulin, 0.6 nmol/l tumor necrosis factor alpha (TNFalpha), and 100 nmol/l dexamethasone reduced galectin-12 gene expression between 47% and 85%. These negative effects were dose-dependent with significant inhibition detectable at concentrations as low as 10 nmol/l isoproterenol, 0.06 nmol/l TNFalpha, and 1 nmol/l dexamethasone. Furthermore, the inhibitory effect of isoproterenol could be almost completely reversed by pretreatment with the beta-adrenergic antagonist propranolol and mimicked by stimulation of G(S)-proteins with cholera toxin or by activation of adenylyl cyclase with forskolin and dibutyryl-cAMP.
Conclusions:
Our results suggest that galectin-12 is an adipocyte-expressed protein which is downregulated by various insulin resistance-inducing hormones. These findings imply a role for galectin-12 in the pathogenesis of insulin resistance.
Insights
Galectin-12, an adipocyte protein, is downregulated by hormones that induce insulin resistance. This suggests galectin-12 plays a role in the development of insulin resistance.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Galectin-12 is an adipocyte-expressed protein.
- It is stimulated by insulin-sensitizing thiazolidinediones.
- Galectin-12 possesses apoptosis-inducing activity.
Purpose of the Study:
- To investigate the regulation of galectin-12.
- To explore galectin-12's potential involvement in insulin resistance development.
Main Methods:
- 3T3-L1 adipocytes were treated with hormones known to impair insulin sensitivity.
- Galectin-12 mRNA levels were quantified using real-time reverse transcription-polymerase chain reaction.
Main Results:
- Hormones like isoproterenol, insulin, tumor necrosis factor alpha (TNFalpha), and dexamethasone significantly reduced galectin-12 gene expression.
- The inhibitory effects were dose-dependent.
- Isoproterenol's inhibition was reversed by propranolol and mimicked by G(S)-protein stimulation or adenylyl cyclase activation.
Conclusions:
- Galectin-12 is downregulated by insulin resistance-inducing hormones in adipocytes.
- These findings suggest a role for galectin-12 in the pathogenesis of insulin resistance.
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