Gpr1 is an active chemerin receptor influencing glucose homeostasis in obese mice

Abstract

Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murine Gpr1 mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) and Cmklr1, Gpr1 expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygous Gpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lacking Gpr1 exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects of Gpr1 deficiency on adiposity, energy balance, and glucose homeostasis in vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity.

CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections

“…Future studies using knockdown approaches could address this point. It is unlikely that GPR1 and APJ serve as coreceptors for SIVagmSab in PBMC, given the low-level function the we found in transfected cells and limited evidence (in humans and rodents at least) for expression on CD4 ϩ T cells (66)(67)(68)(69)(70). Finally, while we tested all of the major alternative coreceptors that have been reported for various SIVs, it is possible that there are other, as-yet-unidentified seven-transmembrane receptor (7TMR) molecules that could also mediate entry.…”

Chemerin in Liver Diseases

“…CMKLR1, G-protein coupled receptor 1 (GPR1) and CC-motif chemokine receptor-like 2 (CCRL2) function as chemerin receptors and bind to chemerin with simi lar affinities [2]. Chemerin activates GPR1 with a higher potency than CMKLR1 showing that GPR1 is a highly sensitive chemerin receptor [10,11]. GPR1 and CCRL2 receptors do not seem to have a role in cell migration [2].…”

“…Chemerin is well known to be expressed in the liver [10,12]. Hepatocytes secrete relatively high concentrations of chemerin which are similar to levels produced by adipocytes.…”

“…Compared to white adipose tissue and skeletal muscle, expression of the chemerin receptors CMKLR1, GPR1 and CCRL2 is low in the rodent liver [10,15]. Chemerin may nevertheless influence the properties of all liver resident cells.…”

La chémérine

“…Celle-ci est activée par clivage de sa partie carboxy-terminale par diffé-rentes enzymes (cathepsine G, plasmine, élastase, ainsi la souris, une invalidation du gène Cmklr1 entraîne une diminution de l'adiposité et une augmentation de l'intolérance au glucose [27] bien que Rouger et al aient observé une augmentation de l'adiposité chez des souris Cmklr1 -/- [28]. L'invalidation de Gpr1, codant le second récepteur de la chémérine, entraîne aussi une intolérance au glucose, mais uniquement au cours d'un régime enrichi en lipides [29]. Comme chez les rongeurs, les niveaux circulants de chémérine chez l'homme sont corrélés positivement avec l'indice de masse corporelle, le taux de triglycérides et les niveaux plasmatiques de cytokines inflammatoires [21,22].…”