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Huyn, F.K., J. Levi, H.C. Denroche, S.L. Gray, P. Voshol, U.H. Neumann, M. Speck, S.C. Chua, S.D. Covey and T.J. Kieffer. 2010. Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance. Diabetes. 59(December):3032-3040.

Number of pages: 9

DOI: 10.2337/db10-0074

Type of document: Journal Article

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More information on authors/freelancers connected to LBI :
Peter Voshol, PhD


Language of document: English

Title in English: Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance

Abstract / summary in English:

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.


Keywords in English: Leptin, Type 2 Diabetes, Metabolic Syndrome, Pre-diabetes, liver, glucose metabolism
Disruption of Hepatic Leptin Signaling Protects Mice From Age- and Diet-Related Glucose Intolerance