Exposure to Nanoplastics During Pregnancy Induces Brown Adipose Tissue Whitening in Male Offspring

Abstract

Background: Polystyrene nanoplastics (PSNPs) have been recognized as emerging environmental pollutants with potential health impacts, particularly on metabolic disorders. However, the mechanism by which gestational exposure to PSNPs induces obesity in offspring remains unclear. This study, focused on the whitening of brown adipose tissue (BAT), aims to elucidate the fundamental mechanisms by which prenatal exposure to PSNPs promotes obesity development in mouse offspring.

Methods and results: Pregnant dams were subjected to various doses of PSNPs (0 µg/µL, 0.5 µg/µL, and 1 µg/µL), and their offspring were analyzed for alterations in body weight, adipose tissue morphology, thermogenesis, adipogenesis, and lipophagy. The findings revealed a notable reduction in birth weight and an increase in white adipocyte size in adult offspring mice. Notably, adult male mice exhibited BAT whitening, correlated with a negative dose-dependent downregulation of UCP1 expression, indicating thermogenesis dysfunction. Further investigation revealed augmented lipogenesis evidenced by the upregulation of FASN, SREBP-1c, CD36, and DGAT2 expression, coupled with the inhibition of lipophagy, indicated by elevated levels of mTOR, AKT, and p62 proteins and reduced levels of LC3II/LCI and Lamp2 proteins in male offspring.

Conclusions: These findings indicate that gestational PSNP exposure plays a role in the development of obesity in offspring through the whitening of brown adipose tissue, which is triggered by lipogenesis and lipophagy inhibition, providing a novel insight into the metabolic risks associated with gestational PSNPs exposure.

Keywords: brown adipose tissue whitening; lipogenesis; lipophagy; obesity; polystyrene nanoplastics; pregnancy.

Figure 1

Effect of prenatal PSNPs exposure on outcomes of newborns. (A) Animal model; (B) body weight before mating; (C) number of pups per litter; (D) sex ratio of newborn mice per litter; (E) birth weight of offspring. n = 22–24/group. Compared to the control group, * p < 0.05, and *** p < 0.001. Data tables show the p-values from the two-way ANOVA analyses for the factors ‘Sex’ and ‘Dose’. For comparisons between female and male groups, ^# p < 0.05.

Figure 2

Effect of prenatal PSNPs exposure on the development of obesity in adult offspring. (A) Body weight of adult offspring mice (female: n = 14–15/group, male: n = 11–15/group); (B) HE staining of white adipose tissue in adult offspring mice (n = 3/group); (C) quantification of HE staining of white adipose tissue in adult offspring mice (n = 3/group). Compared to the control group, * p < 0.05, and ** p < 0.01. Data tables show the p-values from the two-way ANOVA analyses for the factors ‘Sex’ and ‘Dose’. For comparisons between female and male groups, ^## p < 0.01, and ^### p < 0.001.

Figure 3

Effect of prenatal PSNPs exposure on BAT whitening and thermogenesis in adult offspring mice. (A) Wet weight of BAT in adult offspring mice (female: n = 14–15/group, male: n = 11–15/group); (B) BAT organ coefficient for adult offspring mice (female: n = 14–15/group, male: n = 11–15/group); (C) HE staining of BAT (n = 3/group); (D) quantification of BAT cell area based on HE staining (n = 3/group); (E) UCP1 transcription levels in adult offspring mice (n = 6/group); (F) UCP1 protein expression levels in adult offspring mice (n = 6/group); (G) quantification of UCP1 protein expression levels in adult offspring mice (n = 6/group). Compared to the control group, * p < 0.05, ** p < 0.01, and *** p < 0.001. Data tables show the p-values from the two-way ANOVA analyses for the factors ‘Sex’ and ‘Dose’. For comparisons between female and male groups, ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001.

Figure 4

Effect of prenatal PSNPs exposure on lipogenesis: (A) protein levels of lipid-synthesis-related genes in brown adipose tissue of adult male offspring mice (n = 6/group) and (B) quantification of protein levels of lipid-synthesis-related genes in brown adipose tissue of adult male offspring mice (n = 6/group). Compared to the control group, ** p < 0.01, and *** p < 0.001.

Figure 5

Effect of prenatal PSNPs exposure on lipophagy in BAT of adult male offspring mice. (A) ATGL mRNA levels in the brown adipose tissue of adult male offspring mice; (B) HSL mRNA levels in the brown adipose tissue of adult male offspring mice; (C) protein expression levels of lipophagy-related genes; (D) quantification of protein expression levels of lipophagy-related genes; (E) protein levels of mTOR and AKT in brown adipose tissue of adult male offspring mice; (F) quantification of mTOR and AKT protein levels in brown adipose tissue of adult male offspring mice. n = 6/group. Compared to the control group, * p < 0.05, ** p < 0.01, and *** p < 0.001.