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Updated: May 19, 2026
Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance
R Palanivel1, M D Fullerton, S Galic
1Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON, Canada L8N 3Z5.
Aims/Hypothesis:
Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known.
Methods:
We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed.
Results:
The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1).
Conclusions/Interpretation:
These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.
Insights
Inhibiting suppressor of cytokine signalling-3 (SOCS3) in female mice adipose tissue improves insulin sensitivity during obesity. This highlights SOCS3 as a potential therapeutic target for metabolic disorders.
Area of Science:
- Metabolic Regulation
- Obesity Research
- Adipose Tissue Biology
Background:
- Obesity-induced inflammation elevates suppressor of cytokine signalling-3 (SOCS3) in adipose tissue.
- The role of SOCS3 in whole-body insulin sensitivity in obesity remains unclear.
Purpose of the Study:
- To investigate the physiological importance of adipose tissue SOCS3 in regulating insulin sensitivity in diet-induced obesity.
- To determine if genetic inhibition of SOCS3 in adipose tissue impacts glucose homeostasis and insulin sensitivity.
Main Methods:
- Generated adipose tissue-specific SOCS3 knockout (Socs3 AKO) mice and wild-type (WT) littermates.
- Mice were fed a high-fat diet (HFD) for 16 weeks, with assessments of body mass, adiposity, glucose tolerance, and insulin sensitivity.
- Utilized computed tomography (CT), hyperinsulinaemic-euglycaemic clamps, and positron emission tomography (PET) imaging.
Main Results:
- High-fat diet increased adipose tissue SOCS3 in WT but not Socs3 AKO mice.
- Female Socs3 AKO mice exhibited improved glucose tolerance, lower fasting glucose and insulin levels on HFD compared to WT.
- Enhanced insulin sensitivity in female Socs3 AKO mice was attributed to increased adipose tissue glucose uptake, mediated by improved insulin receptor substrate-1 (IRS1) signaling.
Conclusions:
- Adipose tissue-specific inhibition of SOCS3 production improves whole-body insulin sensitivity in female mice with diet-induced obesity.
- These findings identify SOCS3 in adipose tissue as a key regulator of metabolic health and a potential therapeutic target.
