BACKGROUND: Epidemiologic data have shown that obesity independently increases colorectal cancer (CRC) risk, but the mechanisms are poorly understood. Obesity is an inflammatory state, and chronic colonic inflammation induces CRC. OBJECTIVE: We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss. DESIGN: We measured inflammatory cytokines, gene arrays, and macrophage infiltration in rectosigmoid mucosal biopsies of 10 obese premenopausal women [mean ± SD body mass index (in kg/m(2)): 35 ± 3.5] before and after weight loss induced by a very-low-calorie diet. RESULTS: Subjects lost a mean (±SD) of 10.1 ± 1% of their initial weight. Weight loss significantly reduced fasting blood glucose, total cholesterol, triglycerides, LDL, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 concentrations (P < 0.05). After weight loss, rectosigmoid biopsies showed a 25-57% reduction in TNF-α, IL-1β, IL-8, and monocyte chemotactic protein 1 concentrations (P < 0.05). T cell and macrophage counts decreased by 28% and 42%, respectively (P < 0.05). Gene arrays showed dramatic down-regulation of proinflammatory cytokine and chemokine pathways, prostaglandin metabolism, and the transcription factors STAT3 (signal transducer and activator of transcription 3) and nuclear transcription factor κB. Weight loss reduced expression of FOS and JUN genes and down-regulated oxidative stress pathways and the transcription factors ATF (activating transcription factor) and CREB (cyclic AMP response element-binding). CONCLUSIONS: Our data show that diet-induced weight loss in obese individuals reduces colorectal inflammation and greatly modulates inflammatory and cancer-related gene pathways. These data imply that obesity is accompanied by inflammation in the colorectal mucosa and that diet-induced weight loss reduces this inflammatory state and may thereby lower CRC risk.
BACKGROUND: Epidemiologic data have shown that obesity independently increases colorectal cancer (CRC) risk, but the mechanisms are poorly understood. Obesity is an inflammatory state, and chronic colonic inflammation induces CRC. OBJECTIVE: We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss. DESIGN: We measured inflammatory cytokines, gene arrays, and macrophage infiltration in rectosigmoid mucosal biopsies of 10 obese premenopausal women [mean ± SD body mass index (in kg/m(2)): 35 ± 3.5] before and after weight loss induced by a very-low-calorie diet. RESULTS: Subjects lost a mean (±SD) of 10.1 ± 1% of their initial weight. Weight loss significantly reduced fasting blood glucose, total cholesterol, triglycerides, LDL, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 concentrations (P < 0.05). After weight loss, rectosigmoid biopsies showed a 25-57% reduction in TNF-α, IL-1β, IL-8, and monocyte chemotactic protein 1 concentrations (P < 0.05). T cell and macrophage counts decreased by 28% and 42%, respectively (P < 0.05). Gene arrays showed dramatic down-regulation of proinflammatory cytokine and chemokine pathways, prostaglandin metabolism, and the transcription factors STAT3 (signal transducer and activator of transcription 3) and nuclear transcription factor κB. Weight loss reduced expression of FOS and JUN genes and down-regulated oxidative stress pathways and the transcription factors ATF (activating transcription factor) and CREB (cyclic AMP response element-binding). CONCLUSIONS: Our data show that diet-induced weight loss in obese individuals reduces colorectal inflammation and greatly modulates inflammatory and cancer-related gene pathways. These data imply that obesity is accompanied by inflammation in the colorectal mucosa and that diet-induced weight loss reduces this inflammatory state and may thereby lower CRC risk.
Authors: Zora Djuric; D Kim Turgeon; Ananda Sen; Jianwei Ren; Kirk Herman; Devon Ramaswamy; Lili Zhao; Mack T Ruffin; Daniel P Normolle; William L Smith; Dean E Brenner Journal: Cancer Prev Res (Phila) Date: 2017-11-13
Authors: Keith I Block; Charlotte Gyllenhaal; Leroy Lowe; Amedeo Amedei; A R M Ruhul Amin; Amr Amin; Katia Aquilano; Jack Arbiser; Alexandra Arreola; Alla Arzumanyan; S Salman Ashraf; Asfar S Azmi; Fabian Benencia; Dipita Bhakta; Alan Bilsland; Anupam Bishayee; Stacy W Blain; Penny B Block; Chandra S Boosani; Thomas E Carey; Amancio Carnero; Marianeve Carotenuto; Stephanie C Casey; Mrinmay Chakrabarti; Rupesh Chaturvedi; Georgia Zhuo Chen; Helen Chen; Sophie Chen; Yi Charlie Chen; Beom K Choi; Maria Rosa Ciriolo; Helen M Coley; Andrew R Collins; Marisa Connell; Sarah Crawford; Colleen S Curran; Charlotta Dabrosin; Giovanna Damia; Santanu Dasgupta; Ralph J DeBerardinis; William K Decker; Punita Dhawan; Anna Mae E Diehl; Jin-Tang Dong; Q Ping Dou; Janice E Drew; Eyad Elkord; Bassel El-Rayes; Mark A Feitelson; Dean W Felsher; Lynnette R Ferguson; Carmela Fimognari; Gary L Firestone; Christian Frezza; Hiromasa Fujii; Mark M Fuster; Daniele Generali; Alexandros G Georgakilas; Frank Gieseler; Michael Gilbertson; Michelle F Green; Brendan Grue; Gunjan Guha; Dorota Halicka; William G Helferich; Petr Heneberg; Patricia Hentosh; Matthew D Hirschey; Lorne J Hofseth; Randall F Holcombe; Kanya Honoki; Hsue-Yin Hsu; Gloria S Huang; Lasse D Jensen; Wen G Jiang; Lee W Jones; Phillip A Karpowicz; W Nicol Keith; Sid P Kerkar; Gazala N Khan; Mahin Khatami; Young H Ko; Omer Kucuk; Rob J Kulathinal; Nagi B Kumar; Byoung S Kwon; Anne Le; Michael A Lea; Ho-Young Lee; Terry Lichtor; Liang-Tzung Lin; Jason W Locasale; Bal L Lokeshwar; Valter D Longo; Costas A Lyssiotis; Karen L MacKenzie; Meenakshi Malhotra; Maria Marino; Maria L Martinez-Chantar; Ander Matheu; Christopher Maxwell; Eoin McDonnell; Alan K Meeker; Mahya Mehrmohamadi; Kapil Mehta; Gregory A Michelotti; Ramzi M Mohammad; Sulma I Mohammed; D James Morre; Vinayak Muralidhar; Irfana Muqbil; Michael P Murphy; Ganji Purnachandra Nagaraju; Rita Nahta; Elena Niccolai; Somaira Nowsheen; Carolina Panis; Francesco Pantano; Virginia R Parslow; Graham Pawelec; Peter L Pedersen; Brad Poore; Deepak Poudyal; Satya Prakash; Mark Prince; Lizzia Raffaghello; Jeffrey C Rathmell; W Kimryn Rathmell; Swapan K Ray; Jörg Reichrath; Sarallah Rezazadeh; Domenico Ribatti; Luigi Ricciardiello; R Brooks Robey; Francis Rodier; H P Vasantha Rupasinghe; Gian Luigi Russo; Elizabeth P Ryan; Abbas K Samadi; Isidro Sanchez-Garcia; Andrew J Sanders; Daniele Santini; Malancha Sarkar; Tetsuro Sasada; Neeraj K Saxena; Rodney E Shackelford; H M C Shantha Kumara; Dipali Sharma; Dong M Shin; David Sidransky; Markus David Siegelin; Emanuela Signori; Neetu Singh; Sharanya Sivanand; Daniel Sliva; Carl Smythe; Carmela Spagnuolo; Diana M Stafforini; John Stagg; Pochi R Subbarayan; Tabetha Sundin; Wamidh H Talib; Sarah K Thompson; Phuoc T Tran; Hendrik Ungefroren; Matthew G Vander Heiden; Vasundara Venkateswaran; Dass S Vinay; Panagiotis J Vlachostergios; Zongwei Wang; Kathryn E Wellen; Richard L Whelan; Eddy S Yang; Huanjie Yang; Xujuan Yang; Paul Yaswen; Clement Yedjou; Xin Yin; Jiyue Zhu; Massimo Zollo Journal: Semin Cancer Biol Date: 2015-12 Impact factor: 15.707