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.