RT Journal Article
SR Electronic
T1 Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000898
DO 10.26508/lsa.202000898
VO 4
IS 4
A1 Lea Bühler
A1 Adriano Maida
A1 Elena Sophie Vogl
A1 Anastasia Georgiadi
A1 Andrea Takacs
A1 Oliver Kluth
A1 Annette Schürmann
A1 Annette Feuchtinger
A1 Christine von Toerne
A1 Foivos-Filippos Tsokanos
A1 Katarina Klepac
A1 Gretchen Wolff
A1 Minako Sakurai
A1 Bilgen Ekim Üstünel
A1 Peter Nawroth
A1 Stephan Herzig
YR 2021
UL https://www.life-science-alliance.org/content/4/4/e202000898.abstract
AB Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.