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Department of Pharmacology and Experimental Therapeutics Faculty Papers

2016

Obesity

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Role Of A Plausible Nuisance Contributor In The Declining Obesity-Mortality Risks Over Time., Tapan Mehta, Nicholas M. Pajewski, Scott W. Keith, Kevin Fontaine, David B. Allison Dec 2016

Role Of A Plausible Nuisance Contributor In The Declining Obesity-Mortality Risks Over Time., Tapan Mehta, Nicholas M. Pajewski, Scott W. Keith, Kevin Fontaine, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: Recent analyses of epidemiological data including the National Health and Nutrition Examination Survey (NHANES) have suggested that the harmful effects of obesity may have decreased over calendar time. The shifting BMI distribution over time coupled with the application of fixed broad BMI categories in these analyses could be a plausible "nuisance contributor" to this observed change in the obesity-associated mortality over calendar time.

OBJECTIVE: To evaluate the extent to which observed temporal changes in the obesity-mortality association may be due to a shifting population distribution for body mass index (BMI), coupled with analyses based on static, broad BMI categories. …


Obesity-Induced Colorectal Cancer Is Driven By Caloric Silencing Of The Guanylin-Gucy2c Paracrine Signaling Axis., Jieru E. Lin, Francheska Colon-Gonzalez, Erik S. Blomain, Gilbert W. Kim, Amanda Aing, Brian Stoecker, Justin Rock, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Michal Tomczak, Richard S. Blumberg, Scott A. Waldman Jan 2016

Obesity-Induced Colorectal Cancer Is Driven By Caloric Silencing Of The Guanylin-Gucy2c Paracrine Signaling Axis., Jieru E. Lin, Francheska Colon-Gonzalez, Erik S. Blomain, Gilbert W. Kim, Amanda Aing, Brian Stoecker, Justin Rock, Adam E. Snook, Tingting Zhan, Terry M. Hyslop, Michal Tomczak, Richard S. Blumberg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations …