Abstract | AIM: The aim of this study was to further explore the time-dependent changes in leptin sensitivity using a rat model of dietary fat-induced obesity and to investigate the potential mechanisms governing these changes. METHODS: RESULTS: After 2 weeks of feeding HF diet, there was an increase in total energy intake (TEI) but a reduction in food intake as measured by the mass of food ingested. Body weight at this time was not significantly different between the two diet groups; however, white adipose tissue (WAT) weight was significantly greater in the HF-fed rats than in the chow-fed rats. In addition, spontaneous physical activity levels were increased, but no changes were observed in resting energy expenditure. Furthermore, chow-fed lean rats responded to central leptin administration by reducing the energy intake by approximately 67 kJ compared with saline treatment (p < 0.05), while the HF-fed diet-induced obese (DIO) rats responded by reducing their energy intake by approximately 197 kJ compared with saline treatment (p < 0.05). After 5 weeks of feeding HF diet, TEI remained significantly higher, body weight was significantly increased by 5% in the HF-fed rats and WAT weight was significantly heavier in HF-fed rats than in the chow-fed lean rats. After leptin treatment, the chow-fed lean rats reduced their energy intake by approximately 97 kJ (p < 0.05); yet, leptin had no significant effect in the HF-fed DIO rats. ObRb protein expression, STAT-3 phosphorylation levels, content and messenger RNA ( mRNA) expression of NPY, SOCS-3 mRNA and protein expression and energy intake response to central alpha-MSH administration were not altered after HF diet feeding. CONCLUSION: These results suggest that early in the course of HF diet-induced weight gain, there was a period of central leptin hypersensitivity, and as the obesity progresses, central leptin insensitivity develops. This insensitivity does not appear to be explained by a downregulation of ObRb protein levels, reduced leptin signalling, an increase in either SOCS-3 or NPY expression or reduced function of the melanocortin system. The effect of an HF diet on other actions of leptin such as its effect on the endocannabinoid system should be investigated.
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Authors | B C Fam, M J Morris, M J Hansen, M Kebede, S Andrikopoulos, J Proietto, A W Thorburn |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 9
Issue 6
Pg. 840-52
(Nov 2007)
ISSN: 1462-8902 [Print] England |
PMID | 17924866
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dietary Fats
- Leptin
- Proteins
- Receptors, Leptin
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Topics |
- Adipose Tissue
(metabolism)
- Animals
- Dietary Fats
(administration & dosage, adverse effects)
- Energy Intake
- Energy Metabolism
(physiology)
- Leptin
(administration & dosage, blood, metabolism)
- Male
- Models, Animal
- Obesity
(etiology, metabolism)
- Proteins
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Receptors, Leptin
(blood, metabolism)
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