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Sex-dependent differences in rat brown adipose tissue mitochondrial biogenesis and insulin signaling parameters in response to an obesogenic diet

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Abstract

Marked sex-dependent differences in mitochondrial function and redox status have been found in brown adipose tissue (BAT) of control rats. Insulin also plays a role in the development and maintenance of this tissue. The aim was to investigate sexual dimorphism in the effects of diet-induced obesity on BAT mitochondrial function, as well as on insulin signaling pathway. 10-week-old Wistar rats of both sexes were fed a control diet or a palatable high-fat diet for 26 weeks. Serum markers of insulin sensitivity were analyzed. Mitochondrial DNA (mtDNA) content, mitochondrial oxidative activities, PGC-1α mRNA levels, as well as the protein levels of insulin receptor subunit β (IRβ), glucose transporter GLUT4, β3-adrenergic receptor (β3-AR), phosphatidylinositol 3-kinase, mitochondrial transcription factor A (TFAM), cytochrome c oxidase subunit IV (COX IV), and uncoupling protein 1 (UCP1) were measured in BAT. Obese females showed impaired systemic insulin sensitivity accompanied by diminished IRβ, GLUT4, and β3-AR protein levels in BAT. In addition, TFAM and COX IV protein and PGC-1α mRNA levels decreased in obese females, whereas mtDNA levels increased. In obese males, oxidative and thermogenic capacities rose and no significant changes were observed in the insulin signaling pathway elements. The reduction of the insulin signaling pathway in BAT of obese females may be responsible, at least partially, for the impaired biogenesis process, which could favor the increase of body weight found in this sex. In contrast, the enhanced mitochondrial functionality in the BAT of males would avoid increased oxidative damage and the impairment of insulin signaling.

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Acknowledgments

This work was supported by grants from Dirección General de Investigación y Gestión del Plan Nacional de I + D + i (SAF2010-21792) and Fondo de Investigaciones Sanitarias (PI060293) of the Spanish Government and funds from Comunitat Autònoma de les Illes Balears and FEDER (31/2011). A. Nadal-Casellas was funded by a grant from the Comunitat Autònoma de les Illes Balears. We thank Dr. Hidetoshi Inagaki for providing the antiserum against TFAM.

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Grup de Metabolisme Energètic i Nutrició, Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Cra. Valldemossa km 7.5, 07122, Palma, Spain

    A. Nadal-Casellas, M. Bauzá-Thorbrügge, A. M. Proenza, M. Gianotti & I. Lladó

  2. Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III http://www.ciberobn.es/

    A. Nadal-Casellas, M. Bauzá-Thorbrügge, A. M. Proenza, M. Gianotti & I. Lladó

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  1. A. Nadal-Casellas
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  2. M. Bauzá-Thorbrügge
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  3. A. M. Proenza
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Correspondence to M. Gianotti.

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Nadal-Casellas, A., Bauzá-Thorbrügge, M., Proenza, A.M. et al. Sex-dependent differences in rat brown adipose tissue mitochondrial biogenesis and insulin signaling parameters in response to an obesogenic diet. Mol Cell Biochem 373, 125–135 (2013). https://doi.org/10.1007/s11010-012-1481-x

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  • DOI: https://doi.org/10.1007/s11010-012-1481-x

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