New insights into the inter-organ crosstalk mediated by ChREBP

Figures

• 

  Figure 1. In health, ChREBP drives inter-organ communication through the regulation of different signaling factors in response to glucose and fructose. In the liver, ChREBP promotes the production of bile acids which are released in the intestine facilitating digestion and improving glucose homeostasis by GLP-1. ChREBP activity also triggers hepatokine secretion, such as FGF21, ANGPTL3, ANGPTL8, HGFAC, PANDER, SMOC1 and S100A6. These hormones reach their target tissues via the circulation and acts in specific tissues to regulate metabolic homeostasis. Finally, adipose ChREBP improves local and systemic insulin resistance by releasing PAHSAs.

• 

  Figure 2. In disease, signaling factors levels are dysregulated due to altered activity of ChREBP. In the liver, ChREBP contributes to hepatic steatosis through direct stimulation of the lipogenic pathway. This is more notable in the case of fructose overconsumption, which accelerates the process via direct metabolization in the liver and acetate formation, a lipogenic substrate, by the microbiota in the intestine. At the periphery, ChREBP modulates the alteration in bile acids levels and composition, impairing dietary lipids absorption and GLP-1 secretion. Changes in ChREBP-dependent hepatokines levels are strongly associated to hepatic and systemic insulin resistance. Finally, in adipocytes, PAHSA secretion is decreased due to decreased ChREBP activity, which contributes to the insulin resistant state and disease development.