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Animal Models

Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure

Abstract

Background/Objectives:

Stearoyl-CoA desaturase-2 (SCD2) is the main δ9 desaturase expressed in the central nervous system. Because of its potential involvement in controlling whole-body adiposity, we evaluated the expression and function of SCD2 in the hypothalami of mice.

Subjects/Methods:

Male mice of different strains were used in real-time PCR, immunoblot and metabolic experiments. In addition, antisense oligonucleotides and lentiviral vectors were used to reduce and increase the expression of SCD2 in the hypothalamus.

Results:

The level of SCD2 in the hypothalamus is similar to other regions of the central nervous system and is ~10-fold higher than in any other region of the body. In the arcuate nucleus, SCD2 is expressed in proopiomelanocortin and neuropeptide-Y neurons. Upon high fat feeding, the level of hypothalamic SCD2 increases. Inhibition of hypothalamic SCD2 as accomplished by two distinct approaches, an antisense oligonucleotide or a short-hairpin RNA delivered by a lentivirus, resulted in reduced body mass gain mostly due to increased energy expenditure and increased spontaneous activity. Increasing hypothalamic SCD2 by a lentivirus approach resulted in no change in body mass and food intake.

Conclusions:

Thus, SCD2 is highly expressed in the hypothalami of rodents and its knockdown reduces body mass due to increased whole-body energy expenditure.

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Acknowledgements

We thank Dr E. Roman, Mr J. G. Ferraz and Mr M. Cruz, from the University of Campinas, for technical assistance. The support for the study was provided by Sao Paulo Research Foundation and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. The Laboratory of Cell Signaling belongs to the Obesity and Comorbidities Research Center and National Institute of Science and Technology—Diabetes and Obesity.

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Correspondence to L A Velloso.

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de Moura, R., Nascimento, L., Ignacio-Souza, L. et al. Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure. Int J Obes 40, 471–478 (2016). https://doi.org/10.1038/ijo.2015.188

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