摘要：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
+
Lepr
loxTB/loxTB
) had better glycemic control as they aged compared to male mice with whole-body transcriptional blockade of
Lepr (
Lyz2Cre
−
Lepr
loxTB/loxTB
). In contrast,
Lyz2Cre
+
Lepr
loxTB/loxTB
females only had a trend for diminished hyperglycemia after a prolonged fast. During glucose tolerance tests,
Lyz2Cre
+
Lepr
loxTB/loxTB
males had a mildly improved plasma glucose profile compared to
Cre
−
controls while
Lyz2Cre
+
Lepr
loxTB/loxTB
females had a similar glucose excursion to their
Cre
−
controls. Myeloid cell-specific
Lepr knockdown (
Lyz2Cre
+
Lepr
flox/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
+
Lepr
loxTB/loxTB
mice (p = 0.0774) while interleukin 6 (pro-inflammatory) was lower in male
Lyz2Cre
+
Lepr
flox/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.
