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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #417483
Research Project: Diet and Physical Activity Interventions to Promote Health in Models for Obesity-Related Diseases

Location: Dietary Prevention of Obesity-related Disease Research

Title: Resistant starch inhibits high-fat diet-induced oncogenic responses in the colon of C57BL/6 mice

Author
item Zeng, Huawei
item Safratowich, Bryan
item LIU, ZHENHUA - University Of Massachusetts
item Bukowski, Michael

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/2025
Publication Date: 1/7/2025
Citation: Zeng, H., Safratowich, B.D., Liu, Z., Bukowski, M.R. 2025. Resistant starch inhibits high-fat diet-induced oncogenic responses in the colon of C57BL/6 mice. Journal of Nutritional Biochemistry. 139: Article 109838. https://doi.org/10.1016/j.jnutbio.2025.109838.
DOI: https://doi.org/10.1016/j.jnutbio.2025.109838

Interpretive Summary: Epidemiological studies have shown a linkage between over nutrition, diet-related obesity and increased risk of inflammation and cancer in the colon. In contrast, increasing dietary fiber consumption is associated with lower colon cancer incidence. However, the mechanisms underlying the relationship remains to be elucidated. We hypothesize that increasing fiber intake may reduce the risk of obesity-related inflammation and cancer in the colon. In this study, we demonstrated that resistant starch reduced several biochemical markers and bacterial species (in the feces) which were related to colon inflammation and cancer in a mouse model fed with a high-fat diet. These data provide further insights into the anticancer potential of resistant starch against obesity-related colon cancer and will be useful for scientists who are interested in diet and colon cancer prevention.

Technical Abstract: The beneficial effects of dietary fiber for colon health may be due to short chain fatty acids (SCFAs), such as butyrate, produced by colonic bacterial fermentation. In contrast, obesogenic diet induced obesity is linked to increased colon cancer incidence. We hypothesize that increasing fiber intake promotes healthy microbiome and reduces bacterial dysbiosis and oncogenic signaling in the colon of mice fed an obesogenic diet. Four-week-old male C57BL/6 mice were assigned to 5 dietary groups (n=22 / group) for 24 weeks:(1) AIN93G as a control diet (AIN); (2) a high fat diet (HFD, 45% energy fat); (3) HFD+5% resistant starch (RS) from corn; (4) HFD+10%RS; or (5) HFD+20%RS. Compared to the AIN group, mice receiving the HFD exhibited more than 15% increase in body mass and body fat composition irrespective of RS dosage. However, the HFD+RS groups exhibited an increase (> 300%) of fecal butyrate but a decrease (> 45%) of secondary bile acids in a RS dose-dependent manner over the HFD group. Similarly, there were concomitant decreases (= 25%) in pro-inflammatory plasma cytokines (TNF alpha, IL-6 and MCP-1), beta-catenin and Ki67 protein staining in the colon of the HFD+20%RS group relative to the HFD group. Furthermore, the abundance of colonic Proteobacteria, signatures of dysbiosis, was decreased (> 63%) in a RS dose-dependent manner compared to the HFD. Collectively, these data indicate that RS not only increases butyrate but also reduces secondary bile acids, bacterial dysbiosis and beta-catenin in the colon of mice fed with a HFD.