Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

Yan, Haotian; Guo, Hao; Cheng, Dong; Kou, Ruirui; Zhang, Cuili; Si, Jiliang

doi:10.1002/tox.22562

Cited by 9 publications

(7 citation statements)

References 48 publications

(94 reference statements)

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“…During the postprandial state, insulin secretion from pancreatic β‐cells controls systemic plasma glucose homeostasis by promoting anabolic processes in liver cells . Previous reports have shown that phosphorylation of IRS1 at Ser 307, which antagonizes Akt‐ser 473 phosphorylation, leads to IR and increased plasma glucose . In our experiments, Res relieved ER stress and ROS generation and restored TiO 2 NP‐stimulated phosphorylation of IRS1 and Akt to normal levels.…”

Section: Discussionsupporting

confidence: 55%

“…17,18 Previous reports have shown that phosphorylation of IRS1 at Ser 307, which antagonizes Akt-ser 473 phosphorylation, leads to IR and increased plasma glucose. 19,20 In our experiments, Res relieved ER stress and ROS generation and CYP enzymes expressed throughout the human body play a crucial role in human physiology and are involved in drug and xenobiotic metabolism as well as biosynthesis of endogenous molecules. 21,22 During the CYP catalytic cycle, ROS is generated through uncoupling of the enzymatic cycle.…”

Section: Tio 2 Nps Induce Insulin Resistance and Elevation Of Plasmmentioning

confidence: 90%

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Mechanisms of titanium dioxide nanoparticle‐induced oxidative stress and modulation of plasma glucose in mice

Fan

Yao

et al. 2019

Environmental Toxicology

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Titanium dioxide nanoparticles (TiO2 NPs) are reported to increase plasma glucose levels in mice at specific doses. The production and accumulation of reactive oxygen species (ROS) is potentially the most important factor underlying the biological toxicity of TiO2 NPs but the underlying mechanisms are unclear at present. Data from genome‐wide analyses showed that TiO2 NPs induce endoplasmic reticulum (ER) stress and ROS generation, leading to the inference that TiO2 NP‐induced ER stress contributes to enhancement of ROS in mice. Resveratrol (Res) effectively relieved TiO2 NP‐induced ER stress and ROS generation by ameliorating expression of a common set of activated genes for both processes, signifying that ER stress and ROS are closely related. TiO2 NP‐induced ER stress occurred earlier than ROS generation. Upon treatment with 4‐phenylbutyric acid to relieve ER stress, plasma glucose levels tended toward normal and TiO2 NP increased ROS production was inhibited. These results suggest that TiO2 NP‐induced ER stress promotes the generation of ROS, in turn, triggering increased plasma glucose levels in mice. In addition, Res that displays the ability to reduce ER stress presents a dietary polyphenol antioxidant that can effectively prevent the toxicological effects of TiO2 NPs on plasma glucose metabolism.

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Section: Discussionsupporting

confidence: 55%

Section: Tio 2 Nps Induce Insulin Resistance and Elevation Of Plasmmentioning

confidence: 90%

Mechanisms of titanium dioxide nanoparticle‐induced oxidative stress and modulation of plasma glucose in mice

Fan

Yao

et al. 2019

Environmental Toxicology

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“…Multiple obesogens have been shown to have an effect on these hormones. TBT increases plasma leptin levels in mice, causing an overexpression of the leptin gene, and decreased serum adiponectin levels [71,72]. DEHP decreases both adiponectin and leptin mRNA levels in mice [60].…”

Section: Hormone Interferencementioning

confidence: 99%

Mechanisms of action, chemical characteristics, and model systems of obesogens

et al. 2020

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There is increasing evidence for the role of environmental endocrine disrupting contaminants, coined obesogens, in exacerbating the rising obesity epidemic. Obesogens can be found in everyday items ranging from pesticides to food packaging. Although research shows that obesogens can have effects on adipocyte size, phenotype, metabolic activity, and hormone levels, much remains unknown about these chemicals. This review will discuss what is currently known about the mechanisms of obesogens, including expression of the PPARs, hormone interference, and inflammation. Strategies for identifying obesogenic chemicals and their mechanisms through chemical characteristics and model systems will also be discussed. Ultimately, research should focus on improving models to discern precise mechanisms of obesogenic action and to test therapeutics targeting these mechanisms.

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“…TBT is considered a prototypical obesogen (27)(28)(29)(30)(31). In zebrafish and other teleosts, TBT promotes the accumulation of lipids in different tissues and organs (32,(81)(82)(83)(84)(85)(86)(87)(88).…”

Section: Discussionmentioning

confidence: 99%

Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine

Mueller

et al. 2021

Preprint

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The chemical obesogen tributyltin (TBT) is known to promote fat storage in adipose tissue through direct action on vertebrate cells. TBT also has direct toxic effects on microorganisms, raising the possibility that TBT may also promote fat storage in vertebrates by altering their microbiota. Here we show that exposure of conventionally-reared post-embryonic zebrafish to TBT results in increased adiposity, reduced body size, and altered intestinal microbiota composition including reduced relative abundance of Plesiomonas bacteria. To test if those microbiota alterations affected host adiposity, we exposed conventionally-reared zebrafish to intestinal bacterial strains representative of TBT-altered taxa. We found that introduction of a Plesiomonas strain into conventionally-reared zebrafish was sufficient to reduce adiposity and alter intestinal microbiota composition. Using new long-term gnotobiotic zebrafish husbandry methods, we found that colonization of germ-free zebrafish with Plesiomonas was sufficient to reduce host adiposity. Together these results show the leptogenic activity of Plesiomonas on zebrafish hosts, indicating that the ability of TBT to increase adiposity in vivo may be due in part to TBT-mediated modification of the abundance of leptogenic bacteria like Plesiomonas. These findings underscore how complex reciprocal interactions between animals and their microbial and chemical environments can influence energy balance and metabolic health.IMPORTANCEObesogens are environmental chemicals that promote fat storage and are generally thought to exert this effect directly on animal cells. Using zebrafish, we show that the obesogen tributyltin can also promote fat storage by acting upon intestinal microbiota via reduction of bacteria that are sufficient to reduce fat storage.

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Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

Cited by 9 publications

References 48 publications

Mechanisms of titanium dioxide nanoparticle‐induced oxidative stress and modulation of plasma glucose in mice

Mechanisms of titanium dioxide nanoparticle‐induced oxidative stress and modulation of plasma glucose in mice

Mechanisms of action, chemical characteristics, and model systems of obesogens

Tributyltin exposure leads to increased adiposity and reduced abundance of leptogenic bacteria in the zebrafish intestine

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