Objective: The aim of this study was to investigate the role of peroxisome proliferator-activated receptor (PPAR) activation (single PPARα or PPARγ, and dual PPARα/γ) on UCP1-dependent and -independent thermogenic pathways and mitochondrial metabolism in the subcutaneous white adipose tissue of mice fed a high-fat diet.
Methods: Male C57BL/6 mice received either a control diet (10% lipids) or a high-fat diet (HF; 50% lipids) for 12 wk. The HF group was divided to receive the treatments for 4 wk: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg).
Results: The HF group was overweight, insulin resistant, and had subcutaneous white adipocyte dysfunction. Treatment with PPARα and PPARα/γ reduced body mass, mitigated insulin resistance, and induced browning with increased UCP1-dependent and -independent thermogenesis activation and improved mitochondrial metabolism to support the beige adipocyte phenotype.
Conclusion: PPARα and dual PPARα/γ activation recruited UCP1+ beige adipocytes and favored UCP1-independent thermogenesis, yielding body mass and insulin sensitivity normalization. Preserved mitochondrial metabolism emerges as a potential target for obesity treatment using PPAR agonists, with possible clinical applications.
Keywords: Browning; Mitochondria; Obesity; PPAR; Thermogenesis; UCP1.
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