A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors
| Autor: | Keith A. Yagaloff, Linda Ste. Marie, Richard D. Palmiter, Grant I. Miura, Donald J. Marsh |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Leptin
Male medicine.medical_specialty Receptors Peptide Motor Activity Biology Ion Channels Fat pad Mitochondrial Proteins Mice Central melanocortin system Internal medicine Brown adipose tissue medicine Animals Obesity RNA Messenger Receptor Uncoupling Protein 1 Mice Knockout Multidisciplinary Membrane Proteins Biological Sciences medicine.disease Thermogenin Mice Inbred C57BL medicine.anatomical_structure Endocrinology Gene Expression Regulation Receptor Melanocortin Type 4 Female Melanocortin Carrier Proteins |
| Zdroj: | Proceedings of the National Academy of Sciences. 97:12339-12344 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.220409497 |
| Popis: | Melanocortin-4 receptor (Mc4r)-null mice exhibit late-onset obesity. To determine whether aberrant metabolism contributes to the obesity, food consumption by Mc4r-null mice was restricted to (pair-fed to) that consumed by wild-type (WT) mice. Pair-fed Mc4r-null females maintained body weights intermediate to that of WT and nonpair-fed Mc4r-null females, whereas pairfeeding normalized the body weights of Mc4r-null male mice. Fat pad and circulating leptin levels were elevated in both male and female pair-fed Mc4r-null mice compared with WT mice. Oxygen consumption of Mc4r-null mice with similar body weights as WT controls was reduced by 20%. Locomotor activity of young nonobese Mc4r-null males was significantly lower than that of WT males; however, locomotion of young nonobese females was normal. Core body temperature of Mc4r-null mice was normal, and they responded normally to cold exposure. Young nonobese Mc4r-null females were unable to induce uncoupling protein 1 (UCP1) in brown adipose tissue in response to peripheral leptin administration, whereas UCP1 mRNA was increased by 60% in the WT females. These results indicate that Mc4r deficiency enhances caloric efficiency, similar to that seen in the agouti obesity syndrome and in melanocortin-3 receptor-null mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|