Core Concepts
Noncaloric monosaccharides, including L-glucose and mannose, induce excessive sprouting angiogenesis in zebrafish embryos through the downregulation of Foxo1a, which leads to the upregulation of its target gene Marcksl1a.
Abstract
The study established a short-term zebrafish model that exhibits significant excessive angiogenesis, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR) induced by high glucose treatment. Using this model, the researchers examined the effects of noncaloric monosaccharides on blood vessel development and investigated the underlying molecular mechanisms.
Key highlights:
Glucose and noncaloric monosaccharides, including L-glucose, fructose, mannose, ribose, and arabinose, could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs), in zebrafish embryos.
The excessive angiogenesis was caused by the ectopic activation of quiescent endothelial cells (ECs) into tip cells.
Single-cell transcriptomic sequencing analysis revealed an increased ratio of tip cells and proliferating ECs, accompanied by the downregulation of the transcription factor Foxo1a in the ECs of glucose-treated embryos.
Further experiments validated that Foxo1a negatively regulated the expression of its target gene Marcksl1a, and the downregulation of Foxo1a-Marcksl1a signaling pathway mediated the excessive angiogenesis induced by both caloric and noncaloric monosaccharides.
The findings suggest that the consumption of noncaloric monosaccharides may not be a suitable alternative to sugar-sweetened beverages, as they can also induce vascular dysfunction, potentially contributing to the development of diabetic complications.
Stats
Glucose concentration in the embryos treated with high glucose was significantly higher than that in the control group.
The total length of intersegmental vessels (ISVs) was significantly increased in the glucose-treated embryos compared to the control.
The ratio of arterial and capillary ECs and proliferating ECs was increased in the high glucose-treated embryos.
Quotes
"Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood."
"Our results provided new evidence for the negative roles of caloric and noncaloric monosaccharides on vascular development."