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

Background/Objectives:: Stearoyl-CoA desaturase-2 (SCD2) is the main d9 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.