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Table 1 Effect of high-fat diet-induced obesity on intestinal stem cells

From: Obesity and intestinal stem cell susceptibility to carcinogenesis

  Intervention The effects on ISC Mechanism References
1 Sox9-EGFP mice, low-fat chow (14% kcal from fat) or HFD (45% kcal for 20 weeks
Jejunum
Increases ISC number and proliferation, decreased Paneth and goblet cell numbers, no change in EEC Correlated with insulin or IGF1 signaling impairment [22]
2 High-fat diet induced obesity, independent of the high-fat diet Increased crypt depth, villus height, the number of intestinal epithelial stem cells and goblet cells in vivo - [81]
3 HFD (60% fat) for 9–14 months), vs standard chow-fed counterparts Non-stem progenitor intestinal cells gain more stemness features and self-renewal
Lgr5 + ISC numbers in the small intestine and colon was increased
Villous enterocyte numbers was decreased
A 50% increase in the number of Olfm4 + ISCs and 23% decrease in niche Paneth cell numbers
Crypts from the small intestine and colon were further likely to initiate mini-intestines in culture than those from controls
Induce in b-catenin target genes Jag1 and Jag2 (both ligands for Notch signaling) PPAR-δ signaling [77]
5 male Lgr5 + -GFP fed with HFD (45% fat)
vs purified sucrose-matched LFD (10%) for 12 months
Obesity did not effect on ISC proliferation and related pathways (Akt, MAPK, and Wnt) of Lgr5 + ISCs
Pten inactivation alone, or combined with obesity, is insufficient to drive Lgr5 + -ISC-derived tumorigenesis
HFD upregulate fatty acid metabolism and PPAR signaling [91]
6 Wild type male C57BL/6 J mice
HFD (60% fat) in AOM injection (an initiation) model of colorectal cancer vs LFD (10% fat)
Increased aberrant crypt foci (ACF)
Zone of proliferation in the HFD group was significantly larger than the LFD group
  [143]
7 Lgr5-EGFP-IRES-creERT2 transgenic mice. HFD (60% fat) or low fat (10% fat) diet (Research Diets,) for 12 weeks Higher number of Lgr5-GFP + stem cells per crypt Adiponectin signaling [80]
8 Female mice
HFD (60% fat), 20% as carbohydrate and 20% as protein for 14 weeks
In the colon, the length was significantly reduced. Crypt deep decreased. Number of goblet cells decreased. the ISC numbers was increased but crypt function not changed
In small intestine, villi length decreased. Number of ISCs and progenitor cells was increased. And crypts were further likely to form mini‑intestine organoids in a 3D culture
Barrier function of the small intestine is not altered by HFD. The proportion and count of Paneth cells was not altered in the small intestinal crypt derived from organoids
Possibly the inflammatory factors and monocyte chemoattractant protein‑1 (MCP‑1) [79]
9 HFD in Drosophila Induced a transient activation of intestinal stem cells by microbiota Induces JNK signaling in enterocytes, which triggers production of the cytokine upd3, thereby activates STAT signaling in intestinal stem cells [78]
10 Hyperphagia db/db obese mouse model and a HFD-induced obesity mouse model fed with HFD (60% fat) for 8 weeks vs a standard chow diet ISCs division, villi length, and nutrient absorption increased in both models Upregulation of b-catenin protein along with inactivation of glycogen synthase kinase (GSK)-3b and Cyclin-D1, independent of leptin signaling [75]
  HFD (23% fat) vs 5% fat in control feed in a pig model Expanded colon stem cell zone and proliferative zone earlier onset of obesity and insulin resistance. induce inflammation in Proliferative zone, but not the stem cell zone the increase in inflammation mediators (TLR-4, NF-kB, LCN-2 and IL6) induced with intestinal bacterial flora dysbiosis [125]
11 Lgr5-EGFP-iresCreERT2 male and female mice. HFD (60%) vs 10% LFD fed for 3 months HFD induced similar effects on early growth of ISCs in males and females. The ISCs from females showed a greater growth that was independent of obesity and sex steroid hormones
The diet, sex and interaction between diet and sex does not affect lysozyme (Paneth cell marker) and mucin 2 (goblet cell marker). The Lgr5 (IESC marker) expression was upregulated in females than male independent of diet or interaction between diet and sex
The effect not related to sex steroid hormones [135]
12 WSD (Fat 20% with a low vitamin D concentration compare 5%) for 3 months The number of LGR5-ISCs was decreased and the Bmi + ISCs was increased. A complex transcriptional reprogramming including a mutational signature characteristic of replicative damage of human tumors was induced in both stem cell populations Lower intake of vitamin D3 and/or calcium [139]
13 a chow diet or a 1.25% cholesterol diet Improve ISCs function Modulating the levels of dietary cholesterol, which mediates phospholipid remodeling and tumorigenesiss [82]
14 HFD independent of obesity in a xenograft model of colon cancer Induce LGR5 expression, stem cell transformation, and colon carcinogenesis Through a vitamin A-bound serum retinol binding protein 4-stimulated by retinoic acid 6 (RBP4-STRA6) signaling pathway [136]
15 HFD in mice with an APC mutation, Induce proliferation and DNA damage in Lgr5(+) cells. On the other hand, selective activation of intestinal FXR decrease abnormal Lgr5(+) cell proliferation Increased levels of bile acids causing the repression of farnesoid receptor X (FXR), a sensor of nutritional cues in ISCs [87]