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Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset

Obesity-prone rats have normal blood-brain barrier transport but defective central leptin... Rats selectively bred to develop diet-induced obesity (DIO) were compared with those bred to be diet resistant (DR) on a 31% fat high-energy diet with regard to their central leptin signaling and blood-brain barrier (BBB) transport. Peripheral leptin injection (15 mg/kg ip) into lean 4- to 5-wk-old rats produced 54% less anorexia in DIO than DR rats. DIO rats also had 21, 63, and 64% less leptin-induced immunoreactive phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expression in the hypothalamic arcuate, ventromedial, and dorsomedial nuclei, respectively. However, hindbrain leptin-induced nucleus tractus solitarius pSTAT3 and generalized sympathetic (24-h urine norepinephrine) activation were comparable. Reduced central leptin signaling was not due to defective BBB transport since transport did not differ between lean 4- to 5-wk-old DIO and DR rats. Conversely, DIO leptin BBB transport was reduced when they became obese at 23 wk of age on low-fat chow or after 6 wk on high-energy diet. In addition, leptin receptor mRNA expression was 23% lower in the arcuate nuclei of 4- to 5-wk-old DIO compared with DR rats. Thus a preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased. Defects in leptin transport appear to be an acquired defect associated with the development of obesity and possibly age. signal transducer and activator of transcription 3; leptin receptor; sympathetic nervous system; leptin resistance Address for reprint requests and other correspondence: B. E. Levin, Neurology Service (127C), VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095 (E-mail: [email protected] ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Regulatory, Integrative and Comparative Physiology The American Physiological Society

Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6119
eISSN
1522-1490
DOI
10.1152/ajpregu.00393.2003
pmid
12958061
Publisher site
See Article on Publisher Site

Abstract

Rats selectively bred to develop diet-induced obesity (DIO) were compared with those bred to be diet resistant (DR) on a 31% fat high-energy diet with regard to their central leptin signaling and blood-brain barrier (BBB) transport. Peripheral leptin injection (15 mg/kg ip) into lean 4- to 5-wk-old rats produced 54% less anorexia in DIO than DR rats. DIO rats also had 21, 63, and 64% less leptin-induced immunoreactive phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expression in the hypothalamic arcuate, ventromedial, and dorsomedial nuclei, respectively. However, hindbrain leptin-induced nucleus tractus solitarius pSTAT3 and generalized sympathetic (24-h urine norepinephrine) activation were comparable. Reduced central leptin signaling was not due to defective BBB transport since transport did not differ between lean 4- to 5-wk-old DIO and DR rats. Conversely, DIO leptin BBB transport was reduced when they became obese at 23 wk of age on low-fat chow or after 6 wk on high-energy diet. In addition, leptin receptor mRNA expression was 23% lower in the arcuate nuclei of 4- to 5-wk-old DIO compared with DR rats. Thus a preexisting reduction in hypothalamic but not brain stem leptin signaling might contribute to the development of DIO when dietary fat and caloric density are increased. Defects in leptin transport appear to be an acquired defect associated with the development of obesity and possibly age. signal transducer and activator of transcription 3; leptin receptor; sympathetic nervous system; leptin resistance Address for reprint requests and other correspondence: B. E. Levin, Neurology Service (127C), VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095 (E-mail: [email protected] ).

Journal

AJP - Regulatory, Integrative and Comparative Physiology – The American Physiological Society

Published: Jan 1, 2004

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