Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control

Area of Science:

• Endocrinology
• Metabolism
• Molecular Biology

Background:

• Lipocalin proteins are implicated in various diseases and therapies, but lack clinical translation due to complex biology.
• Lipocalin 13 (LCN13), a hepatokine, has been suggested to play a role in glucose regulation and obesity therapy.

Purpose of the Study:

• To investigate the in vivo role of lipocalin 13 (LCN13) in glucose and lipid homeostasis.
• To determine if LCN13 has a therapeutic or gluco-regulatory role in obesity.

Main Methods:

• Investigated LCN13 effects on primary mouse islets in vitro.
• Modulated endogenous LCN13 expression in lean mice.
• Enhanced hepatic LCN13 secretion in diet-induced and genetic obesity models.
• Assessed systemic glucose and lipid metabolism.
• Examined compensatory regulation of other lipocalin family members.

Main Results:

• LCN13 stimulated glucose-dependent insulin secretion and proliferation of primary mouse islets in vitro.
• Inhibition of endogenous LCN13 did not affect glucose or lipid homeostasis in lean mice.
• Enhanced hepatic LCN13 secretion showed no impact on systemic metabolism in obese mice, neither preventively nor therapeutically.
• Neither loss nor enhanced secretion of LCN13 induced compensatory regulation of related lipocalins.

Conclusions:

• The in vivo effects of LCN13 on systemic glucose and lipid metabolism are minimal, despite its in vitro insulinotropic effects.
• Complex regulatory mechanisms at the organismic level likely mitigate the direct impact of LCN13.
• Current data contrast with proposed gluco-regulatory and therapeutic roles of LCN13 in obesity.