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Oral Subacute Exposure to Cadmium LOAEL Dose Induces Insulin Resistance and Impairment of the Hormonal and Metabolic Liver-Adipose Axis in Wistar Rats

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Abstract

Cadmium is a nonessential transition metal considered one of the more hazardous environmental contaminants. The population is chronically exposed to this metal at low concentrations, designated as the LOAEL (lowest observable adverse effect level) dose. We aimed to investigate whether oral subacute exposure to cadmium LOAEL disrupts hormonal and metabolic effects of the liver-adipose axis in Wistar rats. Fifty male Wistar rats were separated into two groups: control (standard normocalorie diet + water free of cadmium) and cadmium (standard normocalorie diet + drinking water with 32.5 ppm CdCl2). After 1 month, zoometry, a serum lipid panel, adipokines, and proinflammatory cytokines were evaluated. Tests of glucose and insulin tolerance (ITT) and insulin resistance were performed. Histological studies on structure, triglyceride distribution, and protein expression of the insulin pathway were performed in the liver and retroperitoneal adipose tissue. In both tissues, the cadmium, triglyceride, glycogen, and proinflammatory cytokine contents were also quantified. The cadmium group developed dyslipidemia, glucose intolerance, hyperinsulinemia, hyperleptinemia, inflammation, and selective insulin resistance in the liver and adipose tissue. In the liver, glycogen synthesis was diminished, while de novo lipogenesis increased, which was associated with low GSK3β-pS9 and strong expression of SREBP-1c. Dysfunctional adipose tissue was observed with hypertrophy and lipolysis, without changes in SREBP-1c expression and low glycogen synthesis. Both tissues accumulated cadmium and developed inflammation. In conclusion, oral subacute cadmium LOAEL dose exposure induces inflammation, insulin signaling modifications, an early insulin resistance stage (insensibility), and impairment of the hormonal and metabolic liver-adipose axis in Wistar rats.

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Acknowledgments

The authors thank Vicerrectoria de Investigación y Posgrado (VIEP; TRMS-NAT19-1) through Ygnacio Martınez Laguna, CONACyT, and the “Sistema Nacional de Investigadores” of Mexico for the financial support of this research project (VESO, 533291) and Dr. Francisco Ramos Collazo (Bioterio “Claude Bernard”, BUAP) for his assistance and the donation of the animals used in this work. We express our gratitude to the Clinical Laboratory “Los Ángeles” for the biochemical determinations. The workgroup is grateful to Jesús Alberto Abrego Maldonado and Álan Josué Rodríguez Velázquez for their help to histological processing and analysis. We thank Professor Thomas Edwards, Ph.D., for editing the English language text.

Funding

CONACyT and the “Sistema Nacional de Investigadores” of Mexico for the financial support of this research project [VESO, 533291].

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Authors and Affiliations

  1. Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, Autonomous University of Puebla, 14 South, FCQ1, University City, C.P.72560, Puebla, Mexico

    Victor Enrique Sarmiento-Ortega, Diana Moroni-González, Brambila Eduardo & Treviño Samuel

  2. Department of Pharmacy, Faculty of Chemistry Science, Autonomous University of Puebla, 22 South, FC91, University City, C.P. 72560, Puebla, Mexico

    Alfonso Díaz

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  1. Victor Enrique Sarmiento-Ortega
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  2. Diana Moroni-González
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  3. Alfonso Díaz
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  4. Brambila Eduardo
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  5. Treviño Samuel
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Contributions

Victor Enrique Sarmiento-Ortega, Eduardo Brambila, and Samuel Treviño designed the study and wrote the protocol. Victor Enrique Sarmiento-Ortega, Alfonso Díaz, Diana Moroni-González, and Samuel Treviño performed the experiments. Victor Enrique Sarmiento-Ortega, Eduardo Brambila, and Samuel Treviño managed the literature searches and analysis. Eduardo Brambila and Diana Moroni-González undertook the statistical analysis. Alfonso Díaz, Victor Enrique Sarmiento-Ortega, Eduardo Brambila, and Samuel Treviño wrote the first draft of the manuscript. All contributing authors have approved the final manuscript.

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Correspondence to Treviño Samuel.

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Sarmiento-Ortega, V.E., Moroni-González, D., Díaz, A. et al. Oral Subacute Exposure to Cadmium LOAEL Dose Induces Insulin Resistance and Impairment of the Hormonal and Metabolic Liver-Adipose Axis in Wistar Rats. Biol Trace Elem Res 200, 4370–4384 (2022). https://doi.org/10.1007/s12011-021-03027-z

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