In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates dysregulation of the lipid metabolism in mouse offspring fed a high-calorie diet

Etsuko Sugai, Wataru Yoshioka, Masaki Kakeyama, Seiichiroh Ohsako, Chiharu Tohyama

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Exposure to environmental chemicals, including dioxins, is a risk factor for type 2 diabetes mellitus in humans. This study explored the hypothesis that in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener among dioxins, aggravates this disease state later in adulthood. Pregnant C57Bl/6J mice were administered either a single oral dose of TCDD (3.0μgkg-1 body weight) or corn oil on gestational day 12.5. The male pups born to these two groups of dams were given either a regular diet or a high-calorie diet, after postnatal day (PND) 28. The four groups of investigated offspring were thus termed T-R (TCDD regular diet), T-H (TCDD high-calorie diet), V-R (vehicle regular diet), and V-H (vehicle high-calorie diet). The mice were regularly monitored for body weight, blood pressure and glucose, until they reached 26weeks of age. Mice in the V-H group were significantly obese at weeks 15 and 26, but they exhibited no diabetes-associated signs of insulin resistance or hypertension. However, metabolic syndrome-related alterations with marginal signs of liver damage were found at week 26. Pronounced signs of dysregulated lipid metabolism with altered gene expression and liver inflammation were already present at week 15, whereas such alterations were suppressed in the T-H group. Although the mechanism is unclear, this study showed that in utero and lactational exposure to low-dose TCDD does not aggravate obesity-induced disease states, such as adult-onset diabetes, but instead attenuates the dysregulation of lipid metabolism brought on by a high-calorie diet.

Original languageEnglish
Pages (from-to)296-306
Number of pages11
JournalJournal of Applied Toxicology
Volume34
Issue number3
DOIs
Publication statusPublished - 2014 Mar
Externally publishedYes

Fingerprint

Nutrition
Lipid Metabolism
Diet
Medical problems
Dioxins
Liver
Body Weight
Corn Oil
Poisons
Blood pressure
Environmental Exposure
Polychlorinated Dibenzodioxins
1,4-dioxin
Gene expression
Type 2 Diabetes Mellitus
Dams
Insulin Resistance
Blood Glucose
Obesity
Insulin

Keywords

  • Dioxin
  • Environmental chemicals
  • Glucose and lipid metabolism
  • Maternal exposure
  • Mouse

ASJC Scopus subject areas

  • Toxicology

Cite this

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates dysregulation of the lipid metabolism in mouse offspring fed a high-calorie diet. / Sugai, Etsuko; Yoshioka, Wataru; Kakeyama, Masaki; Ohsako, Seiichiroh; Tohyama, Chiharu.

In: Journal of Applied Toxicology, Vol. 34, No. 3, 03.2014, p. 296-306.

Research output: Contribution to journalArticle

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abstract = "Exposure to environmental chemicals, including dioxins, is a risk factor for type 2 diabetes mellitus in humans. This study explored the hypothesis that in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener among dioxins, aggravates this disease state later in adulthood. Pregnant C57Bl/6J mice were administered either a single oral dose of TCDD (3.0μgkg-1 body weight) or corn oil on gestational day 12.5. The male pups born to these two groups of dams were given either a regular diet or a high-calorie diet, after postnatal day (PND) 28. The four groups of investigated offspring were thus termed T-R (TCDD regular diet), T-H (TCDD high-calorie diet), V-R (vehicle regular diet), and V-H (vehicle high-calorie diet). The mice were regularly monitored for body weight, blood pressure and glucose, until they reached 26weeks of age. Mice in the V-H group were significantly obese at weeks 15 and 26, but they exhibited no diabetes-associated signs of insulin resistance or hypertension. However, metabolic syndrome-related alterations with marginal signs of liver damage were found at week 26. Pronounced signs of dysregulated lipid metabolism with altered gene expression and liver inflammation were already present at week 15, whereas such alterations were suppressed in the T-H group. Although the mechanism is unclear, this study showed that in utero and lactational exposure to low-dose TCDD does not aggravate obesity-induced disease states, such as adult-onset diabetes, but instead attenuates the dysregulation of lipid metabolism brought on by a high-calorie diet.",
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