Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance
| Autor: | Scott D. Covey, Jasna Levi, Sarah L. Gray, Heather C. Denroche, Madeleine Speck, Timothy J. Kieffer, Ursula H. Neumann, Frank K. Huynh, Peter J. Voshol, Streamson C. Chua |
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| Rok vydání: | 2010 |
| Předmět: |
Leptin
Male Aging medicine.medical_specialty Endocrinology Diabetes and Metabolism Adipokine Adipose tissue Mice Transgenic 030209 endocrinology & metabolism Biology Polymerase Chain Reaction Mice 03 medical and health sciences 0302 clinical medicine Insulin-Secreting Cells Internal medicine Glucose Intolerance Insulin Secretion Internal Medicine medicine Animals Insulin Glucose homeostasis Obesity 030304 developmental biology 0303 health sciences Glucose tolerance test Leptin Deficiency Leptin receptor medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology Glucose Tolerance Test Glucose clamp technique Glucose Metabolism Endocrinology Diabetes Mellitus Type 2 Liver Glucose Clamp Technique Receptors Leptin Female hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db10-0074 |
| Popis: | OBJECTIVE The liver plays a critical role in integrating and controlling glucose metabolism. Thus, it is important that the liver receive and react to signals from other tissues regarding the nutrient status of the body. Leptin, which is produced and secreted from adipose tissue, is a hormone that relays information regarding the status of adipose depots to other parts of the body. Leptin has a profound influence on glucose metabolism, so we sought to determine if leptin may exert this effect in part through the liver. RESEARCH DESIGN AND METHODS To explore this possibility, we created mice that have disrupted hepatic leptin signaling using a Cre-lox approach and then investigated aspects of glucose metabolism in these animals. RESULTS The loss of hepatic leptin signaling did not alter body weight, body composition, or blood glucose levels in the mild fasting or random-fed state. However, mice with ablated hepatic leptin signaling had increased lipid accumulation in the liver. Further, as male mice aged or were fed a high-fat diet, the loss of hepatic leptin signaling protected the mice from glucose intolerance. Moreover, the mice displayed increased liver insulin sensitivity and a trend toward enhanced glucose-stimulated plasma insulin levels. Consistent with increased insulin sensitivity, mice with ablated hepatic leptin signaling had increased insulin-stimulated phosphorylation of Akt in the liver. CONCLUSIONS These data reveal that unlike a complete deficiency of leptin action, which results in impaired glucose homeostasis, disruption of leptin action in the liver alone increases hepatic insulin sensitivity and protects against age- and diet-related glucose intolerance. Thus, leptin appears to act as a negative regulator of insulin action in the liver. |
| Databáze: | OpenAIRE |
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