PPAR-α activation counters brown adipose tissue whitening: a comparative study between high-fat– and high-fructose–fed mice

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2020-10, Vol.78, p.110791-110791, Article 110791
• Main Authors: Miranda, Carolline Santos, Silva-Veiga, Flavia, Martins, Fabiane Ferreira, Rachid, Tamiris Lima, Mandarim-De-Lacerda, Carlos Alberto, Souza-Mello, Vanessa
• Format: Article
• Language: English
• Subjects: Activation; Adipocytes; Adipose tissue; Adipose tissue (brown); Agonists; Animals; Body fat; Body mass; Carbohydrates; Comparative studies; Diet; Droplets; Energy; Euthanasia; Food; Fructose; Gene expression; Glucose; Glucose tolerance; Growth factors; High fat diet; Interscapular brown adipose tissue; Intolerance; Lipid peroxidation; Lipids; Lipolysis; Metabolic rate; Microscopy; Obesity; Oxidation; Peroxisome proliferator-activated receptors; Polymerase chain reaction; PPAR-α; Proteins; Software; Thermogenesis; Vascular endothelial growth factor; Whitening
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2020.110791

•Brown adipocyte dysfunction is called whitening.•Excessive fat, but not fructose, lead to whitened brown adipocyte in mice.•PPAR-α reduced body mass, lessened fat pads, and reduced oral glucose intolerance.•PPAR-α activation tackled whitening by enhancing lipolysis, β-oxidation, and thermogenesis.•PPAR-α rescued brown adipocytes dysfunction by using lipids as fuel for thermogenesis. 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. 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. 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. 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.