Altered hypothalamic leptin, insulin, and melanocortin binding associated with moderate-fat diet and predisposition to obesity.

Full Abstract

Rats with a genetic predisposition to develop diet-induced obesity (DIO) have a preexisting reduction in central leptin and insulin sensitivity. High-fat diets also reduce sensitivity to leptin, insulin, and melanocortin agonists. We postulated that such reduced sensitivities would be associated with decreased binding to the hypothalamic leptin, insulin, and melanocortin receptors in selectively bred DIO rats and in rats fed a high-energy (HE; 31% fat) diet for 7 wk. On HE diet, DIO rats gained 15% more weight and had 121% heavier fat pads and 70% higher leptin levels than low fat chow-fed DIO rats. Diet-resistant (DR) rats gained no more weight on HE diet but had 48% heavier fat pads and 70% higher leptin levels than chow-fed DR rats. Compared with DR rats, DIO (125)I-leptin binding was 41, 36, and 40% lower in the hypothalamic dorsomedial, arcuate, and dorsomedial portion of the ventromedial nuclei, respectively, and arcuate (125)I-insulin binding was 31% lower independent of diet. In contrast, hypothalamic melanocortin binding did not differ between DIO and DR rats. However, HE diet intake lowered lateral hypothalamic melanocortin-3 and melanocortin-4 receptor and hippocampal insulin binding of both DIO and DR rats and hypothalamic paraventricular nucleus melanocortin-4 receptor binding only in DR rats. Neither genotype nor diet affected substantia nigra or ventral tegmental area binding. These results corroborate our previous findings demonstrating a preexisting decrease in DIO hypothalamic leptin and insulin signaling and demonstrate that HE diet intake reduces hypothalamic melanocortin and hippocampal insulin binding.

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Author information

Author/s: Irani, Boman G (BG); Dunn-Meynell, Ambrose A (AA); Levin, Barry E (BE);

Affiliation: Department of Neurology, New Jersey Medical School, Newark, USA.

Grants: DK-30066 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Endocrinology (Endocrinology), published in United States. (Language: eng)

Reference: 2007-Jan; vol 148 (issue 1) : pp 310-6

Dates: Created 2006/12/20; Completed 2007/02/13; Revised 2007/12/03;

PMID: 17023527, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adipose Tissue - metabolism
Animals
Arcuate Nucleus - metabolism
Blood Glucose
Dietary Fats - pharmacology
Dorsomedial Hypothalamic Nucleus - metabolism
Hypothalamus - metabolism
Insulin - blood; pharmacokinetics
Iodine Radioisotopes - diagnostic use
Leptin - blood; pharmacokinetics

Male
Melanocortins - metabolism
Obesity - genetics; metabolism
Rats
Rats, Mutant Strains
Receptor, Melanocortin, Type 4 - metabolism
Substantia Nigra - metabolism
Ventral Tegmental Area - metabolism
Ventromedial Hypothalamic Nucleus - metabolism
Weight Gain - physiology

Associated Chemicals: Blood Glucose (0) ; Dietary Fats (0) ; Iodine Radioisotopes (0) ; Leptin (0) ; Melanocortins (0) ; Receptor, Melanocortin, Type 4 (0) ; Insulin (11061-68-0)

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