Deleterious Effects of Yoyo Dieting and Resistant Starch on Gastrointestinal Morphology

Abstract

Background: Obesity is associated with structural deterioration in the gut. Yoyo dieting, which refers to repeated phases of dieting and non-dieting periods leading to cyclic weight loss and regain, is a common occurrence in individuals with obesity. However, there is limited evidence on how gut structures are affected in yoyo dieting. There is good evidence suggesting that increased intake of resistant starch (RS) may be beneficial in promoting structural improvements in the gut. This investigation aimed to explore the effect of yoyo dieting on gastrointestinal structure and whether RS has beneficial effects in improving obesity-related gastrointestinal damage.

Method: In this study, male and female C57BL/6 mice were assigned to six different diets for 20 weeks: (1) control diet, (2) high fat diet (HF), (3) yoyo diet (alternating HF and control diets every 5 weeks), (4) control diet with RS, (5) HF with RS, and (6) yoyo diet with RS. Distal colon was collected for epithelial barrier integrity measurement. The small and large intestines were collected for histological assessment.

Results: After 20 weeks, yoyo dieting resulted in increased colonic inflammation and exacerbated mucosal damage in comparison with continuous HF diet feeding. RS supplemented in HF and yoyo diets reduced mucosal damage in comparison to diets without RS. However, RS supplementation in a control diet significantly increased inflammation, crypt length, and goblet cell density. There were no significant differences in epithelial change and epithelial barrier integrity across diet groups.

Conclusions: This study suggests that yoyo dieting worsens gut damage, and incorporating high levels of RS may be detrimental in the absence of dietary challenge.

Keywords: gastrointestinal structures; inflammation; resistant starch; weight cycling; yoyo dieting.

Figure 1

20-week dietary treatments.

Figure 2

Small intestinal analysis of inflammatory cell density. Images of inflammatory cell density in male mice (A–F). In male mice, inflammatory cell density of (C) HF mice is greater than (A) control mice. Inflammatory cell count of (E) yoyo mice appears to be in an intermediate state between (A) control and (C) HF states. Higher inflammatory cell count is observed in (B) control RS mice in comparison to (A) control mice. Inflammatory cell density of (D) HF RS mice is increased in comparison to (C) HF mice. Inflammatory cell count of (F) yoyo RS mice is lower than (E) yoyo mice. Statistical analysis of changes in the inflammatory cell density of male and female mice (G), with * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001 used to determine significance. Scale bar = 150 µm. M: male; F: female.

Figure 3

Small intestinal analysis of epithelial change. The epithelial cells in small intestinal crypts across all diet groups appeared to be similar in size. No significant differences were observed between all groups. M: male; F: female.

Figure 4

Small intestinal analysis of mucosal changes in male mice. Intact mucosa in (A) control and (B) control RS mice. Swollen and distorted villi in (C) HF mice. Intact mucosa in (D) HF RS mice. Swollen, distorted and damaged mucosa in (E) yoyo mice but intact mucosa in (F) yoyo RS mice. Statistical analysis of changes in the mucosal architecture of male mice (G), with * p ≤ 0.05 used to determine significance. Scale bar = 150 µm. M: male.

Figure 5

Small intestinal analysis of mucosal changes in female mice. Mucosal damage was observed only in (C) HF mice, with intact mucosa in (A) control, (B) control RS, (D) HF RS, (E) yoyo, and (F) yoyo RS mice. Statistical analysis of changes in the mucosal architecture of female mice (G), with * p ≤ 0.05, ** p ≤ 0.01 used to determine significance. Scale bar = 150 µm. F: female.

Figure 6

Colonic analysis of inflammatory cell density. Images of inflammatory cell density in male mice (A–F). Regardless of sex, inflammatory cell density of (B) control RS mice is higher than (A) control mice. In male mice, inflammatory cell density of (E) yoyo mice is higher than (C) HF and (A) control mice. Inflammatory cell density of (B) control RS and (F) yoyo mice are similar. Inflammatory cell density of (D) HF RS and (F) yoyo RS mice do not differ and are lower than (B) control RS mice. In female mice, the inflammatory cell density of control mice is lower than other groups. Statistical analysis of changes in colonic inflammatory cell density of male and female mice (G), with ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001 used to determine significance. Scale bar = 150 µm. M: male; F: female.

Figure 7

Histological analysis of epithelial change in the colon of male and female mice. Male control RS mice had increased crypt length in comparison to control, HF RS, and yoyo RS mice. Male HF and yoyo mice had similar crypt lengths. No significant differences in epithelial change were observed in female mice. * p ≤ 0.05, ** p ≤ 0.01 used to determine significance. M: male; F: female.

Figure 8

Histological scores of goblet cell change. Male control RS mice had significantly higher goblet cell density compared to control and yoyo RS mice. Male yoyo mice had increased goblet cell density in comparison with control mice. No significant differences were observed in other groups and in female mice. * p ≤ 0.05, *** p ≤ 0.001 used to determine significance. M: male; F: female.

Figure 9

Colonic epithelial barrier integrity measured in Ussing chambers. No significant differences were observed between all groups. M: male; F: female.