Search for an Endogenous Bombesin-Like Receptor 3 (BRS-3) Ligand Using Parabiotic Mice

Bombesin-like receptor 3 (BRS-3) is an X-linked G protein-coupled receptor involved in the regulation of energy homeostasis. Brs3 null (Brs3 (-/y)) mice become obese. To date, no high affinity endogenous ligand has been identified. In an effort to detect a circulating endogenous BRS-3 ligand, we generated parabiotic pairs of mice between Brs3 (-/y) and wild type (WT) mice or between WT controls. Successful parabiosis was demonstrated by circulatory dye exchange. The Brs3 (-/y)-WT and WT-WT pairs lost similar weight immediately after surgery. After 9 weeks on a high fat diet, the Brs3 (-/y)-WT pairs weighed more than the WT-WT pairs. Within the Brs3 (-/y)-WT pairs, the Brs3 (-/y) mice had greater adiposity than the WT mice, but comparable lean and liver weights. Compared to WT mice in WT-WT pairs, Brs3 (-/y) and WT mice in Brs3 (-/y)-WT pairs each had greater lean mass, and the Brs3 (-/y) mice also had greater adiposity. These results contrast to those reported for parabiotic pairs of leptin receptor null (Lepr (db/db)) and WT mice, where high leptin levels in the Lepr (db/db) mice cause the WT parabiotic partners to lose weight. Our data demonstrate that a circulating endogenous BRS-3 ligand, if present, is not sufficient to reduce adiposity in parabiotic partners of Brs3 (-/y) mice.