(22-12-10) Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.

Pendyala S, Neff LM, Su?rez-Fari?as M, Holt PR.

Clinical and Translational Science Center, The Rockefeller University, New
York, NY, and St Luke's Roosevelt Hospital Center, New York, NY.
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 (MCP-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.

Source: Am J Clin Nutr. 2010 Dec 8.

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