Chronic exposure to a mixture of phthalates shifts the white and brown adipose tissue phenotypes in female mice

Jones B Graceli, Charles S Da Costa, Mary J Laws, Ashley R K Deviney, Daryl Meling, Jodi A Flaws

Research output: Contribution to journalArticlepeer-review

Abstract

Phthalates are endocrine-disrupting chemicals used in consumer products. Although phthalates are obesogens and affect metabolic function, it is unknown if chronic exposure for 6 months to a phthalate mixture alters adipose tissue phenotype in female mice. After vehicle or mixture exposure, white adipose tissue and brown adipose tissue (WAT and BAT) were analyzed for expression of adipogenesis, proliferation, angiogenesis, apoptosis, oxidative stress, inflammation, and collagen deposition markers. The mixture altered WAT morphology, leading to an increase in hyperplasia, blood vessel number, and expression of BAT markers (Adipoq and Fgf2) in WAT. The mixture increased the expression of the inflammatory markers, Il1β, Ccl2, and Ccl5, in WAT. The mixture also increased expression of the proapoptotic (Bax and Bcl2) and antiapoptotic (Bcl2l10) factors in WAT. The mixture increased expression of the antioxidant Gpx1 in WAT. The mixture changed BAT morphology by increasing adipocyte diameter, whitening area, and blood vessel number and decreased expression of the thermogenic markers Ucp1, Pgargc1a, and Adrb3. Furthermore, the mixture increased the expression of adipogenic markers Plin1 and Cebpa, increased mast cell number, and increased Il1β expression in BAT. The mixture also increased expression of the antioxidant markers Gpx and Nrf2 and the apoptotic marker Casp2 in BAT. Collectively, these data indicate that chronic exposure to a phthalate mixture alters WAT and BAT lipid metabolism phenotypes in female mice, leading to an apparent shift in their normal morphology. Following long-term exposure to a phthalate mixture, WAT presented BAT-like features and BAT presented WAT-like features.

Original languageEnglish (US)
Article numberkfad032
Pages (from-to)204-218
Number of pages15
JournalToxicological Sciences
Volume193
Issue number2
Early online dateApr 6 2023
DOIs
StatePublished - May 31 2023

Keywords

  • phthalates
  • phenotype
  • changes
  • brown adipose tissue
  • white adipose tissue
  • mixture
  • endocrine disruptor

ASJC Scopus subject areas

  • Toxicology

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