Energy-restricted high-fat diets only partially improve markers of systemic and adipose tissue inflammation.

This study aimed at investigating whether the weight loss due to energy-restricted high-fat diets is accompanied with parallel improvements in metabolic markers and adipose tissue inflammation. Eight-week-old C57BL/6J mice were given free access to a low-fat (LF) or a high-fat (45% of energy from fat-HF) diet for 6 months. Restricting intake of the HF diet by 30% (HFR) during the last 2 months of the HF feeding trial decreased fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), and plasma triglyceride levels and improved hepatic steatosis compared to ad libitum HF feeding, indicating an improved metabolic profile. Further, analysis of gonadal white adipose tissue (GWAT) gene expression by microarray and quantitative PCR analyses demonstrated that HFR downregulated expression of genes linked to cell and focal adhesion, cytokine-cytokine receptor interaction, and endoplasmic reticulum (ER)-associated degradation pathway. However, HFR had no effect on circulating plasminogen activator inhibitor-1 (PAI-1) and nonesterified fatty acid levels, which were persistently higher in both HF and HFR groups compared to the LF group. Furthermore, HFR had a negative effect on plasma total adiponectin level. Finally, while HFR decreased GWAT monocyte chemotactic protein-1 (MCP-1), interleukin-2 (IL-2), and PAI-1 levels, it did not affect several other cytokines including granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1β, IL-6, and IL-10. In summary, energy-restricted high-fat diets improve insulin sensitivity, while only partially improving markers of systemic and adipose tissue inflammation. In conclusion, our study supports the recommended low-fat intake for overall cardiovascular health.