Dietary flaxseed oil reduces adipocyte size, adipose monocyte chemoattractant protein-1 levels and T-cell infiltration in obese, insulin-resistant rats

Background: Adipocyte dysfunction is characterized by an increase in adipocyte size and changes to their adipokine profiles. Immune cell infiltration into adipose tissue is thought to contribute to the metabolic complications of obesity, with local and systemic consequences for the inflammatory status of the obese individual. Dietary interventions with omega-3 fatty acids from marine sources have been successful at reducing inflammation. The aim of this study was to determine whether flaxseed oil containing the plant-based omega-3 fatty acid alpha-linolenic acid (ALA) is an effective modulator of inflammation and adipocyte dysfunction. Methods: Seventeen-week old male fa/fa and lean Zucker rats were fed a control diet (faCTL, InCTL) and fa/fa rats were fed an ALA-rich flaxseed oil supplemented diet (faFLAX) for 8 weeks. Adipose tissue and serum were collected and analyzed for cytokine (1-6, 1L-10, IL-18, IL-2, IFN-gamma, TNF-alpha), haptoglobin, monocyte chemoattractant protein-1 (MCP-1) and adipokine (leptin, adiponectin) levels. Splenocytes were isolated and ex vivo mitogen-stimulated cytokine production was measured. Digital images of adipose tissue sections were used to quantify adipocyte area. Macrophage and T-cell infiltration were assessed in adipose tissue by immunohistochemistry. Results: faFLAX rats had 17% smaller adipocytes and 5-fold lower MCP-1 levels in adipose tissue than faCTL rats. Adipose tissue levels of IL-10 were 72% lower in the faFLAX group compared to baseline, and TNF-alpha levels decreased 80% (equal to InCTL levels) in the faFLAX group compared to faCTL There were no changes in ex vivo cytokine production by splenocytes between faFLAX and faCTL. Macrophage infiltration was not different among groups; however, faFLAX rats had less T-cell infiltration than faCTL rats. Conclusions: Dietary intervention with ALA-rich flaxseed oil in obese Zucker rats reduced adipocyte hypertrophy, protein levels of inflammatory markers MCP-1 and TNF-alpha and T-cell infiltration in adipose tissue. Modest improvements to other parameters of obesity were also observed. The results suggest that, due to its ability to improve adipocyte function, ALA-rich flaxseed oil confers health benefits in obesity. (C) 2012 Elsevier Ltd. All rights reserved.