Vanderbilt Institute for Obesity & Metabolism

2011 -12 P&F Awardees


Congratulations to 2011- 2012 P&F Awardees!


Jay H.  FowkePrincipal Investigator: Jay Fowke, PhD, MPH, Department of Medicine


"A Potential Link Between Obesity and Autophagy Toward Prostate Cancer"


Prostate cancer is the second leading cause of cancer-related death among U.S. men, and is increasinglyrecognized as a metabolic diseases associated with obesity, insulin, and inflammation. This pilot projectbegins our long-term plan to investigate the role of autophagy in human prostate cancer risk, progression,and prognosis. Autophagy is a lysosome-dependent process by which cells degrade non-essentialcomponents as a source of energy under times of energy deprivation. This process may be mediatedthrough known energy-sensing pathways, and VUMC investigators recently found autophagy plays animportant role in mouse models of prostate cancer progression. This 1-year pilot study will leverage datafrom the Nashville Men’s Health Study (NMHS; PI: Fowke); our on-going epidemiologic investigation ofprostate cancer. The NMHS contains an extensive biospecimen repository with serum, plasma, urine, andextracted DNA, along with linked datasets involving medical chart review, body size measures , medicationuse, and questionnaire data from over 1,000 prostate cancer cases and 1,000 controls without prostatecancer. Pilot VIOM funding would be used to develop a case-control analysis targeting high-priorityautophagy-related genes and their association with obesity and prostate cancer. We propose two specificaims: (1) determine the association between autophagy-related genetic loci and low-grade and high grade(Gleason>6) prostate cancer in humans; and (2) determine if observed associations between obesity andhigh-grade prostate cancer in humans are mediated by genetic variation in autophagy pathways.

Collaborating investigators bring expertise in genetics and mouse-model studies but are new to obesityresearch. With promising results, future protocols would seek funding to expand the genetic investigation,and include a prostate tissue-based analysis of autophagy. Further research would investigate the impactof autophagy on major issues regarding prostate cancer treatment response, treatment toxicity, weight gain,and survivoral.

Picture of Welch, Edward Principal Investigator:  Edward Brian Welch, PhD, Assistant Professor, Radiology and Radiological Sciences


 "Brown Adipose Tissue Quantification Using Magnetic Resonance Imaging"

 The overall objective of the proposed research is to develop and validate methods for the detection andvolumetric quantification of brown adipose tissue (BAT) using magnetic resonance imaging (MRI). BAT is athermogenic tissue known to be present in human infants. BAT was believed to diminish with age to beessentially undetectable in adults. However, recent 18F-fluorodeoxyglucose (18F-FDG) positron emissiontomography (PET) studies suggest that small but metabolically significant amounts of BAT persist intoadulthood. These studies further suggest an inverse relationship between BAT and obesity, although itremains unclear whether reduced BAT amount and/or activity promotes or results from obesity. Therefore,reliable identification and spatial mapping methods that can distinguish BAT from white adipose tissue(WAT) would provide investigators with a powerful tool with which to study BAT’s influence on bodymetabolism and composition.

We hypothesize that in human adult subjects, BAT will be detectable andquantifiable separately from WAT using MRI approaches that enable quantitative measurement of MR properties of water and lipid protons. We will test this hypothesis by pursuing the following two specfic aims:[1] Develop and optimize MRI measurements of fat signal fraction (FSF), water longitudinal relaxation rate (T1_H2O), and water apparent diffusion coefficient (ADC_H2O) for the volumetric quantification and characterization of BAT in lean athletic adult human subjects who are screened with conventional FWMRI and identified to have conspicuous adipose depots in the anatomical locations typical for BAT. Location(s) and volume of BAT will be confirmed using cold-activated 18F-FDG PET.[2]  Validate MRI measurements of FSF, T1_H2O, and ADC_H2O for prospective detection and volumetric quantification of BAT in adult human subjects who have BMIs in the normal to obese range and significant WAT depots. Location(s) and volume of BAT will be confirmed using cold-activated 18F-FDG PET.