Persistent metabolic toxicities following developmental exposure to hexafluoropropylene oxide trimer acid (HFPO-TA): Roles of peroxisome proliferator activated receptor gamma

• Published in: Journal of hazardous materials 2024-06, Vol.471, p.134337-134337, Article 134337
• Main Authors: Zhong, Shuping, Yuan, Junhua, Niu, Yong, Wang, Siyi, Gong, Xinxian, Ji, Jing, Zhong, Yuxu, Zheng, Yuxin, Jiang, Qixiao
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Chick Embryo; Chicken embryo; Chickens; Fluorocarbons - toxicity; Hexafluoropropylene oxide trimer acid (HFPO-TA); Liver - drug effects; Liver - metabolism; Metabolic toxicities; Pancreas - drug effects; Pancreas - metabolism; Peroxisome proliferator activated receptor gamma (PPARγ); PPAR gamma - genetics; PPAR gamma - metabolism
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.134337

Hexafluoropropylene oxide trimer acid (HFPO-TA), a perfluorooctanoic acid (PFOA) substitute, exhibited strong affinity and capability to activate peroxisome proliferator activated receptor gamma (PPARγ), a lipid metabolism regulator, suggesting potential to induce metabolic toxicities. Fertile chicken eggs were exposed to 0, 0.5, 1 or 2 mg/kg (egg weight) HFPO-TA and incubated until hatch. Serum from 0- and 3- month-old chickens were subjected to liquid chromatography ultra-high resolution mass spectrometry for HFPO-TA concentration, while liver, pancreas and adipose tissue samples were collected for histopathological assessments. In ovo PPARγ reporter and silencing system were established with lentivirus microinjection. qRT-PCR and immunohistochemistry were utilized to evaluate the expression levels of PPARγ downstream genes. In 3-month-old animals developmentally exposed to HFPO-TA, adipose tissue hyperplasia, hepatic steatosis, pancreas islet hypertrophy and elevated serum free fatty acid / insulin levels were observed. Results of reporter assay and qRT-PCR indicated HFPO-TA-mediated PPARγ transactivation in chicken embryo. Silencing of PPARγ alleviated HFPO-TA-induced changes, while PPARγ agonist rosiglitazone mimicked HFPO-TA-induced effects. qRT-PCR and immunohistochemistry revealed that FASN and GPD1 were upregulated following developmental exposure to HFPO-TA in 3-month-old animals. Developmental exposure to HFPO-TA induced persistent metabolic toxicities in chickens, in which PPARγ played a central role. [Display omitted] •Developmental exposure to HFPO-TA induced persistent metabolic toxicities.•HFPO-TA could activate PPARγ in developing chicken embryo.•PPARγ is required for HFPO-TA-induced persistent metabolic toxicities.