Role of myeloid cell leptin signaling in the regulation of glucose metabolism.

Abstract

Although innate immunity is linked to metabolic health, the effect of leptin signaling in cells from the innate immune system on glucose homeostasis has not been thoroughly investigated. We generated two mouse models using Cre-lox methodology to determine the effect of myeloid cell-specific leptin receptor (Lepr) reconstitution and Lepr knockdown on in vivo glucose metabolism. Male mice with myeloid cell-specific Lepr reconstitution (Lyz2Cre+LeprloxTB/loxTB) had better glycemic control as they aged compared to male mice with whole-body transcriptional blockade of Lepr (Lyz2Cre-LeprloxTB/loxTB). In contrast, Lyz2Cre+LeprloxTB/loxTB females only had a trend for diminished hyperglycemia after a prolonged fast. During glucose tolerance tests, Lyz2Cre+LeprloxTB/loxTB males had a mildly improved plasma glucose profile compared to Cre- controls while Lyz2Cre+LeprloxTB/loxTB females had a similar glucose excursion to their Cre- controls. Myeloid cell-specific Lepr knockdown (Lyz2Cre+Leprflox/flox) did not significantly alter body weight, blood glucose, insulin sensitivity, or glucose tolerance in males or females. Expression of the cytokine interleukin 10 (anti-inflammatory) tended to be higher in adipose tissue of male Lyz2Cre+LeprloxTB/loxTB mice (p = 0.0774) while interleukin 6 (pro-inflammatory) was lower in male Lyz2Cre+Leprflox/flox mice (p < 0.05) vs. their respective controls. In conclusion, reconstitution of Lepr in cells of myeloid lineage has beneficial effects on glucose metabolism in male mice.

• Authors: Sandra Pereira, Daemon L Cline, Melissa Chan, Kalin Chai, Ji Soo Yoon, Shannon M O'Dwyer, Cara E Ellis, Maria M Glavas, Travis D Webber, Robert K Baker, Suheda Erener, Scott D Covey, Timothy J Kieffer
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 18394 (09 15 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34526546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Biomarkers
• Blood Glucose
• Leptin
• Glucose

Topics

• Animals
• Biomarkers
• Blood Glucose (metabolism)
• Disease Models, Animal
• Disease Susceptibility
• Energy Metabolism
• Gene Knockdown Techniques
• Glucose (metabolism)
• Homeostasis
• Leptin (genetics, metabolism)
• Male
• Metabolic Diseases (etiology, metabolism)
• Mice
• Myeloid Cells (metabolism)
• Signal Transduction