- The Effect of Leptin Level Fluctuations by a Repeated Fasting/Refeeding on the Leptin Sensitivity in OLETF Rats.
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Sung Chul Park, Yong Hoon Park, So Young Park, Jong Yeon Kim, Yoon Ki Park, Tae Hyung Lee, Kyu Chang Won, Yong Woon Kim
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J Korean Endocr Soc. 2008;23(5):310-318. Published online October 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.5.310
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- BACKGROUND
Leptin resistance is a common feature in obese subjects and animals, and this is commonly accompanied with hyperleptinemia. We speculated that one of the causes of leptin resistance is a persistently elevated leptin concentration and then we hypothesized that fluctuations of serum leptin would increase leptin sensitivity in the leptin-resistant state. METHODS: We used a repeated fasting and refeeding (RFR) protocol to produce fluctuation in leptin levels in 7 month-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats, We then measured the leptin sensitivity following an intracerebroventricular (i.c.v.) infusion of leptin. RESULTS: The OLETF rats exhibited severe visceral fat deposition, hyperleptinemia and leptin resistance. However, in the OLETF-RFR rats, the anorexic effect following i.c.v. leptin infusion was restored. Moreover, the visceral fat mass and serum leptin levels decreased, while the serum adiponectin levels were elevated in the OLETF-RFR rats compared to the OLETF-Control rats. The leptin receptor content in the hypothalamus increased in the OLETF-RFR rats compared to the OLETF-Control rats, and the leptin receptor content in the OLETF-RFR rats decreased compared to that in the the LETO-Control rats. CONCLUSION: These results suggest that the intermittent suppression of the serum leptin level reversed the leptin resistance in OLEFT rats, and this may have occurred due to an increased number of leptin receptors in the hypothalamus.
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Citations
Citations to this article as recorded by  - Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats
Sevag Hamamah, Andras Hajnal, Mihai Covasa
International Journal of Molecular Sciences.2023; 24(11): 9773. CrossRef - Improvement of Leptin Resistance
Yong Woon Kim
Yeungnam University Journal of Medicine.2013; 30(1): 4. CrossRef - The Effect of Food Restriction on Appetite Regulating Hormones and Adiponectin Activity
Ki Hoon Kim, Hyun Kook Kim
Korean Journal of Nutrition.2012; 45(1): 5. CrossRef - The Effect of Leptin Level Fluctuations by a Repeated Fasting/Refeeding on the Leptin Sensitivity in OLETF Rats
Min Seon Kim
Journal of Korean Endocrine Society.2008; 23(5): 298. CrossRef
- Naloxone Increases the Anorexic Effect of MTII in OLETF Rats.
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Jang Ho Bae, Yong Hoon Park, Sung Ho Kim, So Young Park, Jong Yeon Kim, Jo Young Son, Jung Yoon Huh, Kyu Chang Won, Yong Woon Kim
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J Korean Endocr Soc. 2008;23(1):18-26. Published online February 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.1.18
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1,963
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17
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1
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Abstract
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- BACKGROUND
Leptin, an adipocyte-derived hormone, inhibits obesity in lean subjects, but is not widely used because of leptin resistance. Thus, circumventing the arcuate nucleus of the hypothalamus, the site responsible for leptin resistance, has been evaluated for treatment of obesity. However, chronic treatment of melanotan II (MTII), a synthetic agonist of the melanocortin 3/4 receptor, induces tachyphylaxis. Here, we evaluated whether naloxone, a non-specific agouti-related peptide (AgRP) antagonist, increases the anorexic effect of MTII in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: We measured food intake following intracerebroventricular (i.c.v.) infusion of MTII and/or naloxone in OLETF rats. Sprague-Dawley rats were used as a normal control group. RESULTS: The anorexic effect of i.c.v. MTII infusion decreased with time in OLETF rats, indicating the development of tachyphylaxis. In normal control rats, naloxone alone decreased AgRP expression in the hypothalamus but failed to induce anorexia. Moreover, there was no additional anorexic effect with co-treatment of naloxone and MTII. In OLETF rats, naloxone alone did not show an anorexic effect despite increased POMC expression in the hypothalamus. However, naloxone sensitized the anorexic effect of MTII when treated together. CONCLUSION: These results suggest that naloxone augmented the anorexic effect of MTII when treated together in OLETF rats, but had no effect alone. These results suggest that a combination therapy of naloxone and a melanocortin receptor activator would be an effective modality for treatment of obesity.
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Citations
Citations to this article as recorded by - Naloxone Increases the Anorexic Effect of Melanocortin II
Seungjoon Park
Journal of Korean Endocrine Society.2008; 23(1): 15. CrossRef
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