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. 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.
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Authors | Swaroop Pendyala, Lisa M Neff, Mayte Suárez-Fariñas, Peter R Holt |
Journal | The American journal of clinical nutrition
(Am J Clin Nutr)
Vol. 93
Issue 2
Pg. 234-42
(Feb 2011)
ISSN: 1938-3207 [Electronic] United States |
PMID | 21147860
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Blood Glucose
- Cytokines
- Inflammation Mediators
- Lipids
- Transcription Factors
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Topics |
- Adult
- Blood Glucose
(metabolism)
- Cell Count
- Colon
(immunology, metabolism)
- Colorectal Neoplasms
(etiology, genetics, prevention & control)
- Cytokines
(metabolism)
- Diet, Reducing
- Down-Regulation
- Female
- Gene Expression
- Humans
- Inflammation
(diet therapy, etiology, genetics)
- Inflammation Mediators
(metabolism)
- Intestinal Mucosa
(immunology, metabolism)
- Lipids
(blood)
- Macrophages
(physiology)
- Microarray Analysis
- Middle Aged
- Obesity
(complications, diet therapy, physiopathology)
- Premenopause
- Rectum
(immunology, metabolism)
- Risk Factors
- T-Lymphocytes
(physiology)
- Transcription Factors
(metabolism)
- Weight Loss
(physiology)
- Young Adult
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