• Carolline Santos Miranda, Flávia Maria Silva-Veiga, Daiana Araujo Santana-Oliveira, Isabela Macedo Lopes Vasques-Monteiro, Julio Beltrame Daleprane, and Vanessa Souza-Mello.
• Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Biomedical Center, Institute of Biology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
• Nutrition. 2024 Jan 1; 117: 112253112253.

ObjectiveThe 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.MethodsMale 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).ResultsThe 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.ConclusionPPARα 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.Copyright © 2023 Elsevier Inc. All rights reserved.

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