title: Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.
abstract: 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.
  
  
  METHODS
  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.affiliation: Clinical and Translational Science Center, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Swaroop
authors.initials: S
authors.lastname: Pendyala
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Neff
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Peter R
authors.initials: PR
authors.lastname: Holt
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002452:Cell Count; D003106:Colon / Q000276:immunology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004038:Diet, Reducing; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000178:diet therapy* / Q000209:etiology / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000502:physiology; D046228:Microarray Analysis; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000178:diet therapy* / Q000503:physiopathology; D017697:Premenopause; D012007:Rectum / Q000276:immunology / Q000378:metabolism; D012307:Risk Factors; D013601:T-Lymphocytes / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D014157:Transcription Factors