Dataset Information
Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.
Ontology highlight
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.
SUBMITTER: Pendyala S
PROVIDER: S-EPMC3021422 | biostudies-literature | 2011 Feb
REPOSITORIES: biostudies-literature
Publications
Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.
The American journal of clinical nutrition 20101208 2
<h4>Background</h4>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.<h4>Objective</h4>We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss.<h4>Design</h4>We measured inflammatory cytokines, gene arrays, and macrophage infiltra ...[more]
