Progressive brown adipocyte dysfunction: Whitening and impaired nonshivering thermogenesis as long-term obesity complications

• Published in: The Journal of nutritional biochemistry Vol. 105; p. 109002
• Main Authors: Rangel-Azevedo, Camilla, Santana-Oliveira, Daiana Araujo, Miranda, Carolline Santos, Martins, Fabiane Ferreira, Mandarim-de-Lacerda, Carlos Alberto, Souza-Mello, Vanessa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2022
• Subjects: adults; batokines; body temperature; brown adipocytes; brown adipose tissue; dysfunction; energy expenditure; gene expression; glucose; heat production; high fat diet; inflammasomes; inflammation; lipids; males; obesity; thermogenesis; whitening; whitening; thermogenesis; batokines; brown adipose tissue; high-fat diet; obesity; dysfunction
• ISSN: 0955-2863; 1873-4847; 1873-4847
• DOI: 10.1016/j.jnutbio.2022.109002

Chronic obesity damages the cytoarchitecture of brown adipose tissue (BAT), leading to whitening of brown adipocytes and impaired thermogenesis, characterizing BAT dysfunction. Understanding the pathways of whitening progression can bring new targets to counter obesity. This study aimed to evaluate the chronic effect (12, 16, and 20 weeks) of a high-fat diet (50% energy as fat) upon energy expenditure, thermogenic markers, and pathways involved in BAT whitening in C57BL/6J mice. Sixty adult male mice comprised six nutritional groups, where the letters refer to the diet type (control, C or high-fat, HF), and the numbers refer to the period (in weeks) of diet administration: C12, HF12, C16, HF16, C20, and HF20. After sacrifice, biochemical, molecular, and stereological analyses addressed the outcomes. The HF groups had overweight, oral glucose intolerance, and hyperleptinemia, resulting in progressive whitening of BAT and decreased numerical density of nuclei per area of tissue compared to age-matched control groups. In addition, the whitening maximization was related to altered batokines gene expression, decreased nonshivering thermogenesis, and body temperature, resulting in low energy expenditure. The HF20 group showed enlarged adipocytes with stable and dysfunctional lipid droplets, followed by inflammation and ER stress. In conclusion, chronic HF diet intake caused time-dependent maximization of whitening with defective nonshivering thermogenesis. Long-term BAT dysfunction includes down-regulated vascularization markers, upregulated inflammasome activation, and ER stress markers.