OR-76: Selective resistance to central administration of leptin in diet-induced obese mice

Kamal Rahmouni; Donald A Morgan; Allyn L Mark; William G Haynes

doi:10.1016/S0895-7061(03)00159-6

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OR-76: Selective resistance to central administration of leptin in diet-induced obese mice

Journal article

Open access

Peer reviewed

OR-76: Selective resistance to central administration of leptin in diet-induced obese mice

Kamal Rahmouni, Donald A Morgan, Allyn L Mark and William G Haynes

American journal of hypertension, Vol.16(S1), pp.35A-35A

05/2003

DOI: 10.1016/S0895-7061(03)00159-6

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Abstract

We have recently demonstrated that agouti obese mice have selective resistance to leptin, administered peripherally or centrally, with preservation of the sympathetic actions despite loss of the metabolic effects of leptin. In this study, we tested the hypothesis that diet-induced obese mice exhibit selective resistance to centrally administered (intracerebroventricular; ICV) leptin. Mice were instrumented with an ICV cannula one week before the injection. We tested the effects of single ICV administration of 5 mcg of leptin or vehicle on 24 h food intake and body weight and renal sympathetic nerve activity (RSNA) for 4 h in anesthetized mice on high fat diet or normal chow for 10 weeks. While the body weight was comparable at baseline, after 10 weeks body weight was higher (P<0.001) in mice on the high fat diet (29.2±0.6 g) than normal chow (26.5±0.4 g). In mice on normal chow, ICV leptin (n=16) caused a significant decrease in body weight and food intake, respectively, by 3.0±0.3 g (P=0.001) and 2.7±0.2 g (P<0.001). However, in mice on high fat diet ICV leptin (n=16) did not significantly decrease food intake (−1.4±0.2 g, P=0.08) or body weight (−1.8±0.8 g, P=0.6). In contrast, ICV leptin produced comparable increases in RSNA in obese (129±18%, n=13, P<0.001) and lean mice (132±27%, n=10, P<0.001). These data demonstrate selective resistance to the metabolic effects of centrally administered leptin in diet-induced obesity. Our findings suggest that selective leptin resistance in the diet-induced obesity is not due to a defect in leptin transport across the blood brain barrier. Rather, it appears to result from obesity-induced alterations in CNS signaling.

Obesity

sympathetic activity

leptin

Details

Title: Subtitle: OR-76: Selective resistance to central administration of leptin in diet-induced obese mice
Creators: Kamal Rahmouni - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Donald A Morgan - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Allyn L Mark - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
William G Haynes - Hypertension Genetics SCOR, CV Center and Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: American journal of hypertension, Vol.16(S1), pp.35A-35A
DOI: 10.1016/S0895-7061(03)00159-6
ISSN: 0895-7061
eISSN: 1879-1905
Publisher: Oxford University Press
Language: English
Date published: 05/2003
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984072058302771

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