Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

Gustavo W. Fernandes, Cintia B. Ueta, Tatiane L. Fonseca, Cecilia H.A. Gouveia, Carmen L. Lancellotti, Patrícia C. Brum, Marcelo A. Christoffolete, Antonio C. Bianco, Miriam O. Ribeiro

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Three types of beta adrenergic receptors (ARβ1-3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse with Arβ2 knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (47 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and of Arβ1, and Arβ3 mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepatic Pepck (Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and induced Ucp1 expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold-and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalJournal of Endocrinology
Volume221
Issue number3
DOIs
StatePublished - Jun 2014

Keywords

  • Adaptive thermogenesis
  • Brown adipose tissue (BAT)
  • Obesity
  • β-adrenergic receptors

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Fernandes, G. W., Ueta, C. B., Fonseca, T. L., Gouveia, C. H. A., Lancellotti, C. L., Brum, P. C., Christoffolete, M. A., Bianco, A. C., & Ribeiro, M. O. (2014). Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice. Journal of Endocrinology, 221(3), 381-390. https://doi.org/10.1530/JOE-13-0526