Influence of dioxin on the daily variation of insulin sensitivity in mice

Takuma, Masashi; Ushijima, Kazuo; Ando, Hitoshi; Fujimura, Akio

doi:10.1016/j.etap.2015.07.008

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…However, as exposure duration increased glucose tolerance improved, contrary to expectations (Taylor et al, 2013). No changes in insulin levels were observed, consistent with a previous report (Takuma et al, 2015), suggesting insulin signaling is not responsible for improved tolerance. Both adiponectin (ADIPOQ) and FGF21 regulate insulin sensitivity and glucose uptake, with increased ADIPOQ enhancing FGF21-mediated insulin sensitivity (Lin et al, 2013).…”

Section: Discussionsupporting

confidence: 90%

Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD-Elicited Hepatic Fibrosis

Nault¹,

Fader²,

Ammendolia³

et al. 2016

Toxicol. Sci.

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We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis, and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28 d or 92 d. RNA-Seq, ChIP-Seq (2 h), and 28 d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92 d. Additional vehicle and 30 mg/kg treatment groups were allowed to recover for 36 d following the 92-d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92 days, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1b, -2, -4, -6, and -10, as well as TNF-a and IFN-c, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNASeq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. In summary, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.

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Section: Discussionsupporting

confidence: 90%

Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD-Elicited Hepatic Fibrosis

Nault¹,

Fader²,

Ammendolia³

et al. 2016

Toxicol. Sci.

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“…95 The majority of studies relating aryl hydrocarbon receptor ligands to type 2 diabetes have been performed using animal models, such as an experimental study in which dioxin was repeatedly administered to mice to assess its influence on insulin sensitivity. 95 The authors found that activation of aryl hydrocarbon receptor by dioxin caused insulin resistance and an elevated concentration of plasma insulin. 95 Their findings agree with the results of a case-control study in which serum aryl hydrocarbon receptor activity was measured in subjects with type 2 diabetes.…”

Section: Diabetesmentioning

confidence: 99%

“…95 The authors found that activation of aryl hydrocarbon receptor by dioxin caused insulin resistance and an elevated concentration of plasma insulin. 95 Their findings agree with the results of a case-control study in which serum aryl hydrocarbon receptor activity was measured in subjects with type 2 diabetes. There was significantly higher aryl hydrocarbon receptor activity in patients with type 2 diabetes than in age-, sex-, and body mass index-matched subjects presenting impaired glucose tolerance and in healthy controls.…”

Section: Diabetesmentioning

confidence: 99%

“…Tetrachlorodibenzo‐para‐dioxin, or dioxin, is a prototypical aryl hydrocarbon, which, as with other dioxin‐like compounds, binds to aryl hydrocarbon receptor and mediates a variety of toxic effects, such as increased risk of cancer and stroke, suppression of the immune system, hormonal imbalances, and type 2 diabetes 93 . Different studies have reported that aryl hydrocarbon receptor ligands might provoke the development of type 2 diabetes through dioxin‐induced impaired metabolism of glucose, 92 impaired metabolism of glucose by pancreatic beta‐cells, 94 and reduced insulin sensitivity 95 . The majority of studies relating aryl hydrocarbon receptor ligands to type 2 diabetes have been performed using animal models, such as an experimental study in which dioxin was repeatedly administered to mice to assess its influence on insulin sensitivity 95 .…”

Section: Conditions and Behaviors That Stimulate Oxidative Stressmentioning

confidence: 99%

“…Different studies have reported that aryl hydrocarbon receptor ligands might provoke the development of type 2 diabetes through dioxin‐induced impaired metabolism of glucose, 92 impaired metabolism of glucose by pancreatic beta‐cells, 94 and reduced insulin sensitivity 95 . The majority of studies relating aryl hydrocarbon receptor ligands to type 2 diabetes have been performed using animal models, such as an experimental study in which dioxin was repeatedly administered to mice to assess its influence on insulin sensitivity 95 . The authors found that activation of aryl hydrocarbon receptor by dioxin caused insulin resistance and an elevated concentration of plasma insulin 95 .…”

Section: Conditions and Behaviors That Stimulate Oxidative Stressmentioning

confidence: 99%

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Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way

Sczepanik

Grossi

Casati

et al. 2020

Periodontology 2000

346

244

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Periodontitis is a highly prevalent disease. As it progresses, it causes serious morbidity in the form of periodontal abscesses and tooth loss and, in the latter stages, pain. It is also now known that periodontitis is strongly associated with several nonoral diseases. Thus, patients with periodontitis are at greater risk for the development and/or exacerbation of diabetes, chronic obstructive pulmonary disease, and cardiovascular diseases, among other conditions. Although it is without question that specific groups of oral bacteria which populate dental plaque play a causative role in the development of periodontitis, it is now thought that once this disease has been triggered, other factors play an equal, and possibly more important, role in its progression, particularly in severe cases or in cases that prove difficult to treat. In this regard, we allude to the host response, specifically the notion that the host, once infected with oral periodontal pathogenic bacteria, will mount a defense response mediated largely through the innate immune system. The most abundant cell type of the innate immune system – polymorphonuclear neutrophils – can, when protecting the host from microbial invasion, mount a response that includes upregulation of proinflammatory cytokines, matrix metalloproteinases, and reactive oxygen species, all of which then contribute to the tissue damage and loss of teeth commonly associated with periodontitis. Of the mechanisms referred to here, we suggest that upregulation of reactive oxygen species might play one of the most important roles in the establishment and progression of periodontitis (as well as in other diseases of inflammation) through the development of oxidative stress. In this overview, we discuss both innate and epigenetic factors (eg, diabetes, smoking) that lead to the development of oxidative stress. This oxidative stress then provides an environment conducive to the destructive processes observed in periodontitis. Therefore, we shall describe some of the fundamental characteristics of oxidative stress and its effects on the periodontium, discuss the diseases and other factors that cause oxidative stress, and, finally, review potentially novel therapeutic approaches for the management (and possibly even the reversal) of periodontitis, which rely on the use of therapies, such as resveratrol and other antioxidants, that provide increased antioxidant activity in the host.

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