Leptin regulates glucose homeostasis via the canonical Wnt pathway in the zebrafish. Issue 3 (21st February 2022)

• Record Type: Journal Article
• Authors: Kamstra, Kaj; Rizwan, Mohammed Z.; Grattan, David R.; Horsfield, Julia A.; Tups, Alexander
• Is Part Of: FASEB journal. Volume 36:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-21
• Subjects: CRISPR Cas9 -- glucose tolerance test -- leptin receptor -- leptin‐a -- leptin‐b -- lithium chloride; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202101764R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Leptin is best known for its role in adipostasis, but it also regulates blood glucose levels. The molecular mechanism by which leptin controls glucose homeostasis remains largely unknown. Here, we use a zebrafish model to show that Wnt signaling mediates the glucoregulatory effects of leptin. Under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis in zebrafish. In times of nutrient excess, however, we found that leptin also regulates body weight and size. Using a Wnt signaling reporter fish, we show that leptin activates the canonical Wnt pathway in vivo. Utilizing two paradigms for hyperglycemia, it is revealed that leptin regulates glucose homeostasis via the Wnt pathway, as pharmacological inhibition of this pathway impairs the glucoregulatory actions of leptin. Our results may shed new light on the evolution of the physiological function of leptin.