TY - JOUR
T1 - Endothelial leptin receptor mutation provides partial resistance to diet-induced obesity
AU - Pan, Weihong
AU - Hsuchou, Hung
AU - Cornelissen-Guillaume, Germaine G.
AU - Jayaram, Bhavvani
AU - Wang, Yuping
AU - Tu, Hong
AU - Halberg, Franz
AU - Wu, Xiaojun
AU - Chua, Streamson C.
AU - Kastin, Abba J.
PY - 2012/4/15
Y1 - 2012/4/15
N2 - 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 dietinduced obesity.
AB - 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 dietinduced obesity.
KW - Blood-brain barrier
KW - Endothelium
KW - Leptin
KW - Metabolic phenotype
KW - Obesity
KW - Receptor
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U2 - 10.1152/japplphysiol.00590.2011
DO - 10.1152/japplphysiol.00590.2011
M3 - Article
C2 - 22323652
AN - SCOPUS:84860348567
SN - 8750-7587
VL - 112
SP - 1410
EP - 1418
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 8
ER -