Reduced body weight and increased energy expenditure in transgenic mice over-expressing soluble leptin receptor.
BACKGROUND
Soluble leptin receptor (OBRe), one of several leptin receptor isoforms, is the only bona fide leptin binding protein in plasma. Our earlier studies demonstrated that OBRe modulates leptin levels in circulation. Both clinical and in vitro studies have shown that OBRe expression is inversely correlated to body weight and leptin levels. However, it is not clear whether OBRe plays an active role, either in collaboration with leptin or independently, in the maintenance of body weight.


RESULTS
To investigate the function of OBRe in the regulation of energy homeostasis, we generated transgenic mice that express OBRe under the control of human serum amyloid P (hSAP) component gene promoter. The transgene led to approximately doubling of OBRe in circulation in the transgenic mice than in wild type control mice. Transgenic mice exhibited lower body weight at 4 weeks of age, and slower rate of weight gain when compared with control mice. Furthermore, transgenic mice had lower body fat content. Indirect calorimetry revealed that transgenic mice had reduced food intake, increased basal metabolic rate, and increased lipid oxidation, which could account for the differences in body weight and body fat content. Transgenic mice also showed higher total circulating leptin, with the majority of it being in the bound form, while the amount of free leptin is comparable between transgenic and control mice.


CONCLUSIONS
These results are consistent with the role of OBRe as a leptin binding protein in regulating leptin's bioavailability and activity.
Lou
Phing-How
PH
Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Yang
Guoqing
G
Huang
Lu
L
Cui
Yunxia
Y
Pourbahrami
Tiffany
T
Radda
George K
GK
Li
Cai
C
Han
Weiping
W
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D054411:Receptors, Leptin