Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis

• Published in: The American journal of clinical nutrition Vol. 93; no. 2; pp. 234 - 242
• Main Authors: Pendyala, Swaroop, Neff, Lisa M, Suárez-Fariñas, Mayte, Holt, Peter R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.02.2011; American Society for Clinical Nutrition; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: Adult; biochemical pathways; Biological and medical sciences; blood glucose; Blood Glucose - metabolism; blood lipids; carcinogenesis; Cell Count; chemokines; cholesterol; Colon - immunology; Colon - metabolism; Colorectal cancer; colorectal neoplasms; Colorectal Neoplasms - etiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - prevention & control; Cytokines; Cytokines - metabolism; Diet; Diet, Reducing; diet-related diseases; Down-Regulation; Epidemiology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; genes; human diseases; human nutrition; Humans; inflammation; Inflammation - diet therapy; Inflammation - etiology; Inflammation - genetics; Inflammation Mediators - metabolism; interleukin-1; interleukin-8; intestinal mucosa; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Lipids - blood; low density lipoprotein; macrophages; Macrophages - physiology; Menopause; Microarray Analysis; Middle Aged; monocyte chemotactic protein 1; Obesity; Obesity - complications; Obesity - diet therapy; Obesity - physiopathology; Obesity and Eating Disorders; oxidative stress; Premenopause; prostaglandins; Rectum - immunology; Rectum - metabolism; Risk Factors; T-lymphocytes; T-Lymphocytes - physiology; transcription factors; Transcription Factors - metabolism; triacylglycerols; tumor necrosis factor-alpha; Vertebrates: anatomy and physiology, studies on body, several organs or systems; very low calorie diet; Weight control; weight loss; Weight Loss - physiology; Women; Young Adult; Human; Diet; Digestive system; Gut; Weight loss; Rectum; Inflammation; Colon; Carcinogenesis; Feeding
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.110.002683

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/m2): 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.