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- Title
Responsiveness to peripherally administered melanocortins in lean and obese mice.
- Authors
Blüher, Susann; Ziotopoulou, Mary; Bullen Jr., John W.; Moschos, Stergios J.; Ungsunan, Linda; Mantzoros, Christos S.; Kokkotou, Eft; Maratos-Flier, Eleftheria; Blüher, Susann; Bullen, John W Jr; Kokkotou, Efi
- 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, UCPI-DTA) mice. MTII administration (100 µg 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.
- Subjects
CORTIN; MICE; INGESTION; BODY weight; NEUROPEPTIDE Y; OBESITY; LEPTIN
- Publication
Diabetes, 2004, Vol 53, Issue 1, p82
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.1.82