Carolline Santos Miranda1, Flavia Silva-Veiga1, Fabiane Ferreira Martins1, Tamiris Lima Rachid1, Carlos Alberto Mandarim-De-Lacerda1, Vanessa Souza-Mello2. 1. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, the University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. 2. Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, Institute of Biology, the University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: souzamello.uerj@gmail.com.
Abstract
OBJECTIVES: To examine the effects of a selective peroxisome proliferator-activated receptor (PPAR-α) agonist treatment on interscapular brown adipose tissue (iBAT) whitening, focusing on thermogenic, lipolysis, and lipid oxidation markers in mice fed a high-fat or high-fructose diet. METHODS: Fifty animals were randomly assigned to receive a control diet (C, 10% lipids as energy), high-fat diet (HF, 50% lipids as energy), or high-fructose diet (HFRU, 50% fructose as energy) for 12 wk. Each group was redivided to begin the 5-wk treatment, totaling five experimental groups: C, HF, HF-a, HFRU, and HFRU-a. The drug was mixed with diet at the dose of 3.5 mg/kg body mass. RESULTS: HF group was the heaviest group, and the HF and HFRU groups had glucose intolerance. PPAR-α activation alleviated these metabolic constraints. HF and HFRU groups had negative vascular endothelial growth factor A (VEGF-A) immunostaining, but only the HF group had a pattern of lipid droplet accumulation that resembled the white adipose tissue, characterizing the whitening phenomenon. Whitening in the HF group was accompanied by decreased expression of genes related to thermogenesis, β-oxidation, and antiinflammatory effects. All of them were augmented by the PPAR-α activation in HF-a and HFRU-a groups, countering the whitening in the HF-a group. Treated groups also had a lower respiratory exchange ratio than untreated groups, suggesting that lipids were used as fuel for the enhanced thermogenesis. CONCLUSIONS: The PPAR-α agonist countered iBAT whitening by inducing the thermogenic pathway and reducing the lipid droplet size, in addition to enhanced VEGF-A expression, adrenergic stimulus, and lipolysis in HF-fed mice.
OBJECTIVES: To examine the effects of a selective peroxisome proliferator-activated receptor (PPAR-α) agonist treatment on interscapular brown adipose tissue (iBAT) whitening, focusing on thermogenic, lipolysis, and lipid oxidation markers in mice fed a high-fat or high-fructose diet. METHODS: Fifty animals were randomly assigned to receive a control diet (C, 10% lipids as energy), high-fat diet (HF, 50% lipids as energy), or high-fructose diet (HFRU, 50% fructose as energy) for 12 wk. Each group was redivided to begin the 5-wk treatment, totaling five experimental groups: C, HF, HF-a, HFRU, and HFRU-a. The drug was mixed with diet at the dose of 3.5 mg/kg body mass. RESULTS: HF group was the heaviest group, and the HF and HFRU groups had glucose intolerance. PPAR-α activation alleviated these metabolic constraints. HF and HFRU groups had negative vascular endothelial growth factor A (VEGF-A) immunostaining, but only the HF group had a pattern of lipid droplet accumulation that resembled the white adipose tissue, characterizing the whitening phenomenon. Whitening in the HF group was accompanied by decreased expression of genes related to thermogenesis, β-oxidation, and antiinflammatory effects. All of them were augmented by the PPAR-α activation in HF-a and HFRU-a groups, countering the whitening in the HF-a group. Treated groups also had a lower respiratory exchange ratio than untreated groups, suggesting that lipids were used as fuel for the enhanced thermogenesis. CONCLUSIONS: The PPAR-α agonist countered iBAT whitening by inducing the thermogenic pathway and reducing the lipid droplet size, in addition to enhanced VEGF-A expression, adrenergic stimulus, and lipolysis in HF-fed mice.
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