Responsiveness to peripherally administered melanocortins in lean and obese mice.

Abstract

To elucidate mechanisms of melanocortin action, we investigated the effects of a melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 microg q.i.d. i.p.) for 24 h results in similar weight loss but a more pronounced decrease of food intake in DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both food intake and body weight is more pronounced in DIO mice than in lean mice. MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.

• Authors: Susann Blüher, Mary Ziotopoulou, John W Bullen Jr, Stergios J Moschos, Linda Ungsunan, Efi Kokkotou, Eleftheria Maratos-Flier, Christos S Mantzoros
• Journal: Diabetes (Diabetes) Vol. 53 Issue 1 Pg. 82-90 (Jan 2004) ISSN: 0012-1797 [Print] United States
• PMID: 14693701 (Publication Type: Journal Article)

Chemical References

• Leptin
• Neuropeptide Y
• Receptors, Adiponectin
• Receptors, Cell Surface
• adiponectin receptor 1, mouse
• alpha-MSH

Topics

• Animals
• Body Weight (drug effects)
• Energy Intake (drug effects)
• Gene Expression Regulation (drug effects)
• Leptin (pharmacology)
• Liver (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Mice, Obese
• Neuropeptide Y (metabolism)
• Receptors, Adiponectin
• Receptors, Cell Surface (drug effects, genetics)
• Thinness
• Time Factors
• alpha-MSH (pharmacology)