Abstract 109: Leptin Acts in POMC Neurons to Increase Sympathetic Nerve Activity
Leptin acts in the brain to decrease food intake and promote energy expenditure by increasing sympathetic nerve activity (SNA) to thermogenic brown adipose tissue (BAT). Leptin also increases SNA to other beds including kidney with implications for obesity-associated 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 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 (ObR) specifically in POMC neurons (ObRflox/flox/ POMCCre). We used multifiber sympathetic nerve recording to assess the SNA effects of leptin. ObRflox/flox/POMCCre mice exhibited a significantly (P<0.01) blunted renal SNA response to intravenous administration of 120 μg of leptin (4±18%) as compared to wild type controls (161±35%). Intracerebroventricular (ICV) injection of leptin (2 μg) also increased renal SNA in wild type mice (220±77%), but not in ObRflox/flox/POMCCre mice (-1±13%). In contrast, the renal SNA response to ICV insulin (100 μU) was not different (P=0.27) in ObRflox/flox/POMCCre mice (150±24%) as compared to littermate controls (195±68%) demonstrating that the loss of renal SNA response to leptin in mice lacking ObR in POMC neurons is a specific effect. Next, we investigated the requirement of ObR in POMC neurons for the sympathoexcitatory effects of leptin in other beds. Strikingly, ObRflox/flox/POMCCre mice had a significantly (P<0.05) blunted lumbar SNA response to ICV leptin (14±22%) as compared to controls (226±38%). In addition, the BAT SNA response to ICV leptin was attenuated (P<0.01) in ObRflox/flox/POMCCre mice (126±28%) relative to controls (309±80%). These results demonstrate the leptin receptor signaling in POMC neurons in the control of regional sympathetic nerve activity.
- © 2012 by American Heart Association, Inc.