Life Sciences Commons^™

Thrombospondin1 Deficiency Reduces Obesity-Associated Inflammation And Improves Insulin Sensitivity In A Diet-Induced Obese Mouse Model, Yanzhang Li, Xiaopeng Tong, Courtney Rumala, Kate Clemons, Shuxia Wang

Graduate Center for Nutritional Sciences Faculty Publications

BACKGROUND: Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice.

METHODOLOGY/PRINCIPAL FINDINGS: Male TSP1-/- mice …

Srt1720 Improves Survival And Healthspan Of Obese Mice, Robin K. Minor, Joseph A. Baur, Ana P. Gomes, Theresa M. Ward, Anna Csiszar, Evi M. Mercken, Kotb Abdelmohsen, Yu-Kyong Shin, Carles Canto, Morten Scheibye-Knudsen, Melissa Krawczyk, Pablo M. Irusta, Alejandro Martín-Montalvo, Basil P. Hubbard, Yongqing Zhang, Elin Lehrmann, Alexa A. White, Nathan L. Price, William R. Swindell, Kevin J. Pearson, Kevin G. Becker, Vilhelm A. Bohr, Myriam Gorospe, Josephine M. Egan, Mark I. Talan, Johan Auwerx, Christoph H. Westphal, James L. Ellis, Zoltan Ungvari, George P. Vlasuk, Peter J. Elliott, David A. Sinclair, Rafael De Cabo

Graduate Center for Nutritional Sciences Faculty Publications

Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and …