Nutrient-induced intestinal adaption and its effect in obesity

Abstract

Obese and lean individuals respond differently to nutrients with changes in digestion, absorption and hormone release. This may be a result of differences in intestinal epithelial morphology and function driven by the hyperphagia or the type of diet associated with obesity. It is well known that the maintenance and growth of the intestine is driven by the amount of luminal nutrients, with high nutrient content resulting in increases in cell number, villi length and crypt depth. In addition, the type of nutrient appears to contribute to alterations in the morphology and function of the epithelial cells. This intestinal adaptation may be what is driving the differences in nutrient processing in lean versus obese individuals. This review describes how nutrients may be able to induce changes in intestinal epithelial cell proliferation, differentiation and function and the link between intestinal adaptation and obesity.

Keywords: Adaptation; Diet; Intestine; Obesity; Stem cells.

Figure 1

Differences in intestinal morphology. A schematic representation of the crypt-villus structure in lean and obese individuals. Crypt stem cells, CBC/Lgr5 (gray) and +4/Bmi1 (black), continually generate new progenitor cells or transit amplifying (TA) cells. The TA cells divide as they migrate from the crypt to the villus. Differentiation of the TA cells into mature epithelial cell types occurs as the cells exit the crypt and enter into the villus. The goblet cells (oval), enteroendocrine cells (triangle) and enterocytes (rectangle) migrate to the tip of the villus, while the paneth cells (striped) migrate down to the crypt. As depicted, obese individuals have greater villi length, crypt depths and numbers of epithelial cells compared with lean.

Figure 2

Nutrient-induced cell proliferation in the crypt. Nutrients or other secondary factors to diet may directly affect cell proliferation through the canonical Wnt/β-catenin pathway in Lgr5 stem cells or progenitor cells. Glucose has been shown to increase β-catenin through cAMP/PKA pathway and increase β-catenin translocation to the nucleus in other stem cells (see section 3.2). Fatty acids have been shown to increase Wnt ligand availability (see section 3.2). Solid arrows indicate research has documented these signaling mechanism in other stem cell populations. Dashed arrows indicate that there is no current data to support a direct role of nutrients in cell proliferation in progenitor or Bmi1 cells.

Figure 3

Nutrient-induced differentiation in the villi. Differentiation of the epithelial cells types from progenitor cells entails downstream components of Notch signaling. Hes1 activation results in enterocytes, Math1 activation results in goblet cells and ngn3 activation results in enteroendocrine cells. Dashed arrows indicate that it is unknown if nutrients drive changes in these mechanisms.