Perfluorooctanoate (PFOA) cell-autonomously promotes thermogenic and adipogenic differentiation of brown and white adipocytes

• Published in: Ecotoxicology and environmental safety 2024-02, Vol.271, p.115955-115955, Article 115955
• Main Authors: Reckziegel, Patrícia, Petrovic, Natasa, Cannon, Barbara, Nedergaard, Jan
• Format: Article
• Language: English
• Subjects: Adipocytes, White; Adipogenesis; Animals; Caprylates - toxicity; Fluorocarbons; Humans; Mice; Octanoate; PFOA; PPARγ; Thermogenesis; Thermogenesis - genetics
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.115955

Perfluorooctanoic acid (PFOA) is a synthetic organofluoride surfactant associated with several toxic effects in humans and animals. Particularly, it has been observed that PFOA treatment of mice results in weight loss associated with recruited brown adipose tissue (BAT), including an increased amount of uncoupling protein 1 (UCP1). The molecular mechanism behind this BAT recruitment is presently unknown. To investigate the existence of possible cell-autonomous effects of PFOA, we treated primary cultures of brown and white (inguinal) adipocytes with PFOA, or with the non-fluorinated equivalent octanoate, or with vehicle, for 48 h (from day 5 to day 7 of differentiation). PFOA in itself increased the gene expression (mRNA levels) of UCP1 and carnitine palmitoyltransferase 1A (CPT1α) (thermogenesis-related genes) in both brown and white adipocytes. In addition, PFOA increased the expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor α (PPARα) (adipogenesis-related genes). Also the protein levels of UCP1 were increased in brown adipocytes exposed to PFOA. This increase was more due to an increase in the fraction of cells that expressed UCP1 than to an increase in UCP1 levels per cell. The PFOA-induced changes were even more pronounced under simultaneous adrenergic stimulation. Octanoate induced less pronounced effects on adipocytes than did PFOA. Thus, PFOA in itself increased the levels of thermogenic markers in brown and white adipocytes. This could enhance the energy metabolism of animals (and humans) exposed to the compound, resulting in a negative energy balance, leading to diminished fitness. [Display omitted] •How the persistent environmental pollutant PFOA affects exposed organisms is examined.•Cell-autonomous effects of PFOA are seen in primary brown and white adipocyte cultures.•PFOA in itself augments gene expression and protein levels of UCP1 and FABP4.•PFOA augments effects of adrenergic stimulation on gene expression.•PFOA may promote a negative energy balance in exposed animals and humans.