TY - JOUR
T1 - Effect of Weight Gain and Weight Loss on In Vivo Colonocyte Proliferation Rate in People with Obesity
AU - Magkos, Faidon
AU - Sullivan, Shelby
AU - Fitch, Mark
AU - Smith, Gordon
AU - Fabbrini, Elisa
AU - Mittendorfer, Bettina
AU - Hellerstein, Marc
AU - Klein, Samuel
N1 - Funding Information:
Funding agencies: This study was supported by grants DK 101578, DK 94483, DK 56341 (Nutrition Obesity Research Center), DK 20579 (Diabetes Research Center), DK052574 (Digestive Disease Research Center), U54 CA155496 (Transdisciplinary Research on Energetics and Cancer Center), and UL1 RR024992 (Clinical and Translational Science Award) from the National Institutes of Health, a grant from the Pershing Square Foundation, and grants N7337 (Dr. Robert C. and Veronica Atkins Foundation) and 19-900 (UC Berkeley College of Natural Resources). Disclosure: The authors declared no conflict of interest. Author contributions: FM contributed to the study design, performance of the study, data collection, analysis and interpretation, literature search, writing of the manuscript, and approval of the final version to be published. SS performed the sigmoidoscopies and contributed to data interpretation, revising the manuscript for important intellectual content, and approval of the final version to be published. MF contributed to the data analysis, data interpretation, revising the manuscript for important intellectual content, and approval of the final version to be published. GS, EF, and BM contributed to data collection, revising the manuscript for important intellectual content, and approval of the final version to be published. MH and SK contributed to the study design, quality control of analyses, training of personnel, and establishment and maintenance of analytic facilities, data interpretation, and revising the manuscript for content. Clinical trial registration: ClinicalTrials.gov identifiers NCT01538836, NCT01299519, and NCT01184170. Received: 3 July 2017; Accepted: 9 August 2017; Published online in Wiley Online Library. doi:10.1002/oby.21983
Publisher Copyright:
© 2017 The Obesity Society
PY - 2017/11
Y1 - 2017/11
N2 - Objective: To evaluate the effects of diet-induced changes in energy balance and body weight on in vivo colonocyte fractional proliferation rates (FPR) in people with obesity. Methods: In vivo colonocyte FPR was assessed in 31 men and women with obesity (BMI: 35.4 ± 4.0 kg/m2, age: 52.6 ± 8.9 years) before and after diet-induced weight loss, weight gain, or weight maintenance. Subjects ingested aliquots of 2H2O (heavy water) daily for 4 to 7 days, followed by flexible sigmoidoscopy with colon biopsies to assess the incorporation of 2H into the DNA of dividing colonocytes. Results: Colonocyte FPR averaged 12.7% ± 3.8% per day and correlated directly with intra-abdominal adipose tissue (IAAT) volume (r = 0.364, P = 0.044). Colonocyte FPR decreased in the weight loss group, did not change in the weight maintenance group, and increased in the weight gain group. The change in colonocyte FPR correlated directly with the percent change in body weight (r = 0.409, P = 0.028) and IAAT volume (r = 0.598, P = 0.001). Conclusions: A high-calorie diet and weight gain increase, whereas a low-calorie diet and weight loss decrease, in vivo colonocyte proliferation rate in people with obesity. These results suggest that changes in energy balance influence the risk of developing colon cancer in people with obesity by regulating colonic mucosal growth rates.
AB - Objective: To evaluate the effects of diet-induced changes in energy balance and body weight on in vivo colonocyte fractional proliferation rates (FPR) in people with obesity. Methods: In vivo colonocyte FPR was assessed in 31 men and women with obesity (BMI: 35.4 ± 4.0 kg/m2, age: 52.6 ± 8.9 years) before and after diet-induced weight loss, weight gain, or weight maintenance. Subjects ingested aliquots of 2H2O (heavy water) daily for 4 to 7 days, followed by flexible sigmoidoscopy with colon biopsies to assess the incorporation of 2H into the DNA of dividing colonocytes. Results: Colonocyte FPR averaged 12.7% ± 3.8% per day and correlated directly with intra-abdominal adipose tissue (IAAT) volume (r = 0.364, P = 0.044). Colonocyte FPR decreased in the weight loss group, did not change in the weight maintenance group, and increased in the weight gain group. The change in colonocyte FPR correlated directly with the percent change in body weight (r = 0.409, P = 0.028) and IAAT volume (r = 0.598, P = 0.001). Conclusions: A high-calorie diet and weight gain increase, whereas a low-calorie diet and weight loss decrease, in vivo colonocyte proliferation rate in people with obesity. These results suggest that changes in energy balance influence the risk of developing colon cancer in people with obesity by regulating colonic mucosal growth rates.
UR - http://www.scopus.com/inward/record.url?scp=85032499616&partnerID=8YFLogxK
U2 - 10.1002/oby.21983
DO - 10.1002/oby.21983
M3 - Article
C2 - 29086514
AN - SCOPUS:85032499616
VL - 25
SP - S81-S86
JO - Obesity
JF - Obesity
SN - 1930-7381
ER -