Di-(2-ethylhexyl) phthalate increases plasma glucose and induces lipid metabolic disorders via FoxO1 in adult mice

Wei, Xiangjuan; Yang, Daqian; Zhang, Boya; Fan, Xingpei; Du, Hai-Ning; Zhu, Ruijiao; Sun, Xiaotong; Zhao, Meimei; Gu, Ning

doi:10.1016/j.scitotenv.2022.156815

Cited by 15 publications

(7 citation statements)

References 60 publications

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“…In zebrafish larvae, the TBPH burdens were 115.1 ± 33.6, 169.2 ± 47.3, and 880.3 ± 79.5 ng/g dry weight from 0.1, 1.0, and 10 μg/L TBPH treatment groups, respectively. Although the TBPH concentration in surface water is low, it accumulates in aquatic organisms through food web biomagnification . As reported, the TBPH concentration is detected up to 0.13 μg/L in the water of Barcelona, Spain and a maximum of 14.9 ng/g wet weight in white fish from Lake Taihu, China .…”

Section: Resultsmentioning

confidence: 74%

“…Although the TBPH concentration in surface water is low, it accumulates in aquatic organisms through food web biomagnification. 32 As reported, the TBPH concentration is detected up to 0.13 μg/L in the water of Barcelona, Spain 6 and a maximum of 14.9 ng/g wet weight in white fish from Lake Taihu, China. 9 Therefore, the external and internal exposure doses of TBPH used in this study can be considered environmentally relevant concentrations, and our results will provide references to the environmental risk assessments of TBPH.…”

Section: Tbph Concentrations In Exposure Solutions Andmentioning

confidence: 65%

“…70 In addition, oral exposure to DEHP increases plasm glucose and hepatic lipid accumulation in male mice by causing overexpression of the FOXO1 protein, but foxo1 inhibition can protect the mice from these adverse effects. 32 Thus, with a TBPH challenge, the foxo1 factor may be upregulated to promote hepatic lipophagy and FAO, leading to lipid metabolism disorders and hepatotoxicity in the larvae. By Oil Red O staining assays (Figure 6A,B) in the liver tissue and measuring FFA contents (Figure 6C), we determined that the enhanced lipid metabolism and FAO induced by TBPH were reversed by AS1842856.…”

Section: Mediation Role Of the Foxo1mentioning

confidence: 99%

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Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver

Zhou,

Li,

et al. 2024

Environ. Sci. Technol.

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An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

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Section: Resultsmentioning

confidence: 74%

Section: Tbph Concentrations In Exposure Solutions Andmentioning

confidence: 65%

Section: Mediation Role Of the Foxo1mentioning

confidence: 99%

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Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver

Zhou,

Li,

et al. 2024

Environ. Sci. Technol.

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“…Exposure to DEHP might induce glucose metabolic disorder in offspring through the JAK2/STAT3/SOCS3 pathway, which is involved in regulating insulin and leptin signaling pathways (Xu et al, 2018). In addition, DEHP was recently reported to promote the overexpression of FOXO1 to induce insulin resistance and hepatic lipid accumulation (Wei et al, 2022). An overview of the mechanism how exposure to DEHP affect offspring health is summarized in Figure 1.…”

Section: Potential Mechanisms Of Early-life Exposure To Dehp Affectin...mentioning

confidence: 99%

Early-life exposure to di (2-ethyl-hexyl) phthalate: Role in children with endocrine disorders

Zeng

Zhang

Deng

et al. 2023

Front. Cell Dev. Biol.

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Di (2-ethyl-hexyl) phthalate (DEHP), one of endocrine-disrupting chemicals (EDCs), has widespread concern due to its serious health hazards. Exposure to DEHP in the early stage of life affects fetal metabolic and endocrine function, which even would cause genetic lesions. To date, it is widely believed that the increasing incidence of childhood obesity and diabetes in adolescents is related to the impact of DEHP on glucose and lipid homeostasis in children. However, there remains a knowledge gap to recognize these adverse effects. Thus, in this review, besides the exposure routes and levels of DEHP, we further outline the effects of early-life exposure to DEHP on children and potential mechanisms, focusing on the aspect of metabolic and endocrine homeostasis.

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“…Substantially less is known about phthalate interactions with microorganism constituents of the mammalian microbiome. Much of the in vivo evidence to date points to alterations in microbial diversity and accompanying physiological consequences, such as metabolic derangement, [88][89][90][91][92] reproductive organ toxicity, 35,36 and impairments in adaptive immunity. 94 In a multi-rodent study (Wistar Rats, SD rats, BALB/c Mice and C57BL/6J Mice; n = 6 rodents/experimental group or n = 24 rodents per cohort) DEHP was administered at doses of 0, 300, 1000 or 3000 mg/kg/bw/day for 30 days; following sacrifice, organ, and tissue samples were collected, biochemical analyses were performed quantifying testosterone, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum cytokines, cecal/ fecal SCFAs were measured, and 16S rDNA sequencing was performed with paired-end sequencing to assess microbiota diversity.…”

Section: Phthalate-induced Microbial Community Changesmentioning

confidence: 99%

The intestinal microbiota as mediators between dietary contaminants and host health

Cox,

Bomstein,

Jayaraman

et al. 2023

Exp Biol Med (Maywood)

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The gut microbiota sit at an important interface between the host and the environment, and are exposed to a multitude of nutritive and non-nutritive substances. These microbiota are critical to maintaining host health, but their supportive roles may be compromised in response to endogenous compounds. Numerous non-nutritive substances are introduced through contaminated foods, with three common groups of contaminants being bisphenols, phthalates, and mycotoxins. The former contaminants are commonly introduced through food and/or beverages packaged in plastic, while mycotoxins contaminate various crops used to feed livestock and humans alike. Each group of contaminants have been shown to shift microbial communities following exposure; however, specific patterns in microbial responses have yet to be identified, and little is known about the capacity of the microbiota to metabolize these contaminants. This review characterizes the state of existing research related to gut microbial responses to and biotransformation of bisphenols, phthalates, and mycotoxins. Collectively, we highlight the need to identify consistent, contaminant-specific responses in microbial shifts, whether these community alterations are a result of contaminant effects on the host or microbiota directly, and to identify the extent of contaminant biotransformation by microbiota, including if these transformations occur in physiologically relevant contexts.

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Di-(2-ethylhexyl) phthalate increases plasma glucose and induces lipid metabolic disorders via FoxO1 in adult mice

Cited by 15 publications

References 60 publications

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver

Early-life exposure to di (2-ethyl-hexyl) phthalate: Role in children with endocrine disorders

The intestinal microbiota as mediators between dietary contaminants and host health

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