The orphan G protein-coupled receptor, GPR139, is expressed in the hypothalamus and is involved in the regulation of body mass, blood glucose, and insulin.
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2023
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GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system,
including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of
energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the
hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal
hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in
the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic
expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose
levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a
reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a
beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic
GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In
conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its
involvement in the regulation of body mass, blood insulin, and glycemia.
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Obesity, Caloric intake, Energy expenditure, Proopiomelanocortin, G-protein-coupled receptor
Citação
NOGUEIRA, P. A. S. et al. The orphan G protein-coupled receptor, GPR139, is expressed in the hypothalamus and is involved in the regulation of body mass, blood glucose, and insulin. Neuroscience Letters, v. 792, artigo 136955, jan. 2023. Disponível em: <https://www.sciencedirect.com/science/article/pii/S030439402200516X>. Acesso em: 01 ago. 2023.