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Toxicology. 2019 Feb 23;418:41-50. doi: 10.1016/j.tox.2019.02.013. [Epub ahead of print]

Chronic mercury at low doses impairs white adipose tissue plasticity.

Author information

1
Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul, Brazil; Polytechnic School, Federal University of Santa Maria, Av. Roraima, n° 1000, Santa Maria, Rio Grande do Sul, Brazil. Electronic address: danize.rizzetti@gmail.com.
2
Department of Basic Health Sciences, Universidad Rey Juan Carlos, Antenas s/n, Alcorcón, Spain. Electronic address: patricia.corrales@urjc.es.
3
Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul, Brazil. Electronic address: janainapiagette@gmail.com.
4
Histology Laboratory, Universidad Rey Juan Carlos, Antenas s/n, Alcorcón, Spain. Electronic address: jose.uranga@urjc.es.
5
Department of Basic Health Sciences, Universidad Rey Juan Carlos, Antenas s/n, Alcorcón, Spain. Electronic address: gema.medina@urjc.es.
6
Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul, Brazil. Electronic address: franckpecanha@unipampa.edu.br.
7
Cardiac Electromechanical and Vascular Reactivity Laboratory, Universidade Federal do Espírito Santo, Marechal Campos, 1468, Vitória, Espírito Santo, Brazil. Electronic address: daltonv2@outlook.com.
8
Bioactivity and Food Analysis Laboratory, Instituto de Investigación en Ciencias de la Alimentación, Nicolás Cabrera, 9, Campus Universitario de Cantoblanco, Madrid, Spain. Electronic address: marta.miguel@csic.es.
9
Cardiovascular Physiology Laboratory, Universidade Federal do Pampa, BR 472, Km 592, Uruguaiana, Rio Grande do Sul, Brazil. Electronic address: giuliapecanha@unipampa.edu.br.

Abstract

INTRODUCTION:

The toxic effects of mercury (Hg) are involved in homeostasis of energy systems such as lipid and glucose metabolism, and white adipose tissue dysfunction is considered as a central mechanism leading to metabolic disorders.

OBJECTIVE:

The aim of this study was to determine the effects of chronic inorganic Hg exposure at low doses on the lipid and glycemic metabolism.

METHODS:

Male Wistar rats were divided into two groups and treated for 60 days with: saline solution, i.m. (Untreated) and mercury chloride, i.m. - 1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day - (Mercury). Histological analyses, Hg levels measurement and GRP78, CHOP, PPARα, PPARγ, leptin, adiponectin and CD11 mRNA expressions were performed in epididymal white adipose tissue (eWAT). Glucose, triglycerides, total cholesterol and insulin plasma levels were also measured.

RESULTS:

Hg exposure reduced the absolute and relative eWAT weights, adipocyte size, plasma insulin levels, glucose tolerance, antioxidant defenses and increased plasma glucose and triglyceride levels. In addition, CHOP, GRP78, PPARα, PPARγ, leptin and adiponectin mRNA expressions were increased in Hg-treated animals. No differences in Hg concentration were found in eWAT between the untreated and Hg groups. These results suggest that the reduction in adipocyte size is related to the impaired antioxidant defenses, endoplasmic reticulum (ER) stress, the disrupted PPARs and adipokines mRNA expression induced by the metal in eWAT. These disturbances possibly induced a decrease in circulating insulin levels, an imbalance between lipolysis and lipogenesis mechanisms in eWAT, with an increase in fatty acids mobilization, a reduction in glucose uptake and an activation of pro-apoptotic pathways, leading to hyperglycemia and hyperlipidemia.

CONCLUSIONS:

Hg is a powerful environmental WAT disruptor that influences signaling events and impairs metabolic activity and hormonal balance of adipocytes.

KEYWORDS:

Adipokines; Endoplasmic reticulum stress; Lipid and glucose metabolism; Mercury; PPARs; White adipose tissue

PMID:
30807803
DOI:
10.1016/j.tox.2019.02.013

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