Abstract 036: Pomc Neurons, But Not Agrp Neurons, Are Required For Leptin-induced Sympathetic Activation
Leptin acts in the brain to decrease food intake and promote energy expenditure by increasing sympathetic nerve activity (SNA) to thermogenic brown adipose tissue. Leptin also increases SNA to other beds including kidney with implications for obesity-induced hypertension. We previously demonstrated the importance the arcuate nucleus (Arc) of the hypothalamus in mediating leptin-induced increases in regional SNA, but the specific neuronal population within the Arc that mediates these responses is unknown. We hypothesized that agouti-related peptide (AgRP) and/or proopiomelanocortin (POMC) neurons of the Arc are critical for the increases in SNA in response to leptin. To test this, we generated mice lacking the leptin receptor specifically in AgRP or POMC neurons by crossing the LepRflox/flox mice with AgRPCre or POMCCre mice. Consistent with previous reports, both AgRPCre/LepRflox/flox mice and POMCCre/LepRflox/flox mice have a slightly elevated body weight relative to littermate controls. Next, we used multifiber sympathetic nerve recording to assess the SNA effects of leptin. Intracerebroventricular (ICV) injection of leptin (2 μg) led to a comparable increase in renal SNA in control mice (210±93%) and AgRPCre/LepRflox/flox mice (191±53%). AgRPCre/LepRflox/flox mice also displayed a normal lumbar SNA response to ICV leptin (384±86%) relative to controls (325±46%). In contrast, POMCCre/LepRflox/flox mice exhibited a significantly reduced renal SNA response to ICV leptin (5±17%) as compared to controls (174±45%). Lumbar SNA response to leptin was also blunted in POMCCre/LepRflox/flox mice (24±21%) as compared to controls (358±53%). Thus, deletion of the leptin receptor from POMC neurons, but not AgRP neurons, interferes with the ability of leptin to increase sympathetic traffic. These results demonstrate that the sympathetic nerve responses evoked by leptin emanate from leptin action on POMC neurons.
Author Disclosures: B.B. Bell: None. S.M. Harlan: None. D.A. Morgan: None. K. Rahmouni: None.
This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
- © 2014 by American Heart Association, Inc.