Endothelial leptin receptor mutation provides partial resistance to diet-induced obesity.
Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that there is an increased uptake of leptin by brain parenchyma after its delivery by in situ brain perfusion. Here, we tested the hypothesis that endothelial leptin receptor mutation confers partial resistance to diet-induced obesity. These ELKO mice had similar body weight and percent fat as their wild-type littermates when fed with rodent chow, but blood concentrations of leptin were significantly elevated. In response to a high-fat diet, wild-type mice had a greater gain of body weight and fat than ELKO mice. As shown by metabolic chamber measurement, the ELKO mice had higher oxygen consumption, carbon dioxide production, and heat dissipation, although food intake was similar to that of the wild-type mice and locomotor activity was even reduced. This indicates that the partial resistance to diet-induced obesity was mediated by higher metabolic activity in the ELKO mice. Since neuronal leptin receptor knockout mice show obesity and diabetes, the results suggest that endothelial leptin signaling shows opposite effects from that of neuronal leptin signaling, with a facilitatory role in diet-induced obesity.
Blood-Brain Barrier Group, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA. panw@pbrc.edu
Weihong
W
Pan
Hung
H
Hsuchou
Germaine G
GG
Cornelissen-Guillaume
Bhavvani
B
Jayaram
Yuping
Y
Wang
Hong
H
Tu
Franz
F
Halberg
Xiaojun
X
Wu
Streamson C
SC
Chua
Abba J
AJ
Kastin
D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D010101:Oxygen Consumption / Q000502:physiology; D054411:Receptors, Leptin / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D004041:Dietary Fats; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D002245:Carbon Dioxide