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Activation of adipose tissue glycerokinase contributes to increased white adipose tissue mass in mice fed a high-fat diet

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Abstract

Purpose

Investigate the pathways of glycerol-3-P (G3P) generation for triacylglycerol (TAG) synthesis in retroperitoneal (RWAT) and epididymal (EWAT) white adipose tissues from high-fat diet (HFD)-fed mice.

Methods

Mice were fed for 8 weeks a HFD and glycolysis, glyceroneogenesis and direct phosphorylation of glycerol were evaluated, respectively, by 2-deoxyglucose uptake, phosphoenolpyruvate carboxykinase (PEPCK-C) activity and pyruvate incorporation into TAG-glycerol, and glycerokinase activity and glycerol incorporation into TAG-glycerol in both tissues.

Results

HFD increased body and adipose tissue mass and serum levels of glucose and insulin, which were accompanied by glucose intolerance. RWAT and EWAT from HFD-fed mice had increased rates of de novo fatty acid (FA) synthesis (52% and 255%, respectively). HFD increased lipoprotein lipase (LPL) activity and content in EWAT (107%), but decreased in RWAT (79%). HFD decreased the lipolytic response to norepinephrine (57%, RWAT and 25%, EWAT), β3-adrenoceptor content (50%), which was accompanied by a decrease in phosphorylated-hormone-sensitive lipase (~80%) and phosphorylated-adipocyte triacylglycerol lipase (~60%) in both tissues. HFD decreased the in vitro rates of glucose uptake (3.5- and 6-fold), as well as in glyceride-glycerol synthesis from pyruvate (~3.5-fold) without changes in PEPCK-C activity and content in RWAT and EWAT, but increased glycerokinase activity(~3-fold) and content (90 and 40%) in both tissues.

Conclusion

The data suggest that direct phosphorylation of glycerol by glycerokinase may be responsible for maintaining the supply of G3P for the existing rates of FA esterification and TAG synthesis in RWAT and EWAT from HFD-fed mice, contributing, along with a lower lipolytic response to norepinephrine, to higher adiposity.

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Acknowledgements

We are indebted to Neusa M. Zanon, Elza A. Filippin, Lilian C. Heck and Victor D. Galban for their technical assistance.

Author contributions

All authors contributed to the development, analysis and drafting of this article.

Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (310700/2011-6 and 302820/2015-9). S.L.B. received a fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). R.R.V. and G.N.F. received a fellowship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Authors and Affiliations

  1. Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Samyra Lopes Buzelle & Isis do Carmo Kettelhut

  2. Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Franciele Przygodda, Rafael Rossi-Valentim, Graziella Nascimento Ferreira, Maria Antonieta Rissato Garófalo & Luiz Carlos Carvalho Navegantes

  3. Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Vani Maria Alves

  4. Laboratory of Physiology, Federal University of São João del-Rei, Divinópolis, Minas Gerais, Brazil

    Valéria Ernestânia Chaves

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Buzelle, S.L., Przygodda, F., Rossi-Valentim, R. et al. Activation of adipose tissue glycerokinase contributes to increased white adipose tissue mass in mice fed a high-fat diet. Endocrine 69, 79–91 (2020). https://doi.org/10.1007/s12020-020-02288-3

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