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Differential involvement of POMC and AgRP neurons in the regional sympathetic responses to leptin
Author(s) -
Bell Balyssa,
Harlan Shan,
Morgan Donald,
Rahmouni Kamal
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.828.5
Subject(s) - leptin , medicine , endocrinology , proopiomelanocortin , splanchnic , adipose tissue , leptin receptor , hypothalamus , energy homeostasis , arcuate nucleus , arc (geometry) , sympathetic nervous system , biology , chemistry , receptor , obesity , blood pressure , hemodynamics , geometry , mathematics
Leptin action in the brain mediates metabolic homeostasis and promotes energy expenditure by increasing sympathetic nerve activity (SNA) to thermogenic brown adipose tissue (BAT). Leptin also increases SNA to other tissues such as the blood vessels and liver. We previously demonstrated the importance of the hypothalamic arcuate nucleus (Arc) in mediating leptin‐induced increases in regional SNA, but the specific neuronal populations within the Arc that mediate these responses is unknown. We hypothesized that proopiomelanocortin (POMC) and agouti‐related peptide (AgRP) neurons of the Arc differentially mediate regional SNA responses to leptin. To test this, we generated mice lacking leptin receptors in POMC (POMC Cre /LepR fl/fl ) or AgRP neurons (AgRP Cre /LepR fl/fl ). We used multifiber sympathetic nerve recording to assess the effects of intracerebroventricular (ICV) leptin (2 mg) on regional SNA. ICV leptin increased BAT SNA in control mice (326±61%). Interestingly, this response was blunted in both POMC Cre /LepR fl/fl (148±29%, p<0.05) and AgRP Cre /LepR fl/fl mice (172±62%, p<0.05). In contrast, ICV leptin led to a similar increase in splanchnic SNA in control (266±40%) and AgRP Cre /LepR fl/fl mice (214±50%), but the response was reduced in POMC Cre /LepR fl/fl mice (56±38%, p<0.05). Similarly, the renal and lumbar SNA responses to leptin were blunted in POMC Cre /LepR fl/fl , but not in AgRP Cre /LepR fl/fl mice. Conversely, the hepatic SNA response to leptin was reduced in AgRP Cre /LepR fl/fl mice (76±21%, p<0.05), but not in POMC Cre /LepR fl/fl mice (120±49%) relative to controls (196±36%). We concluded that POMC and AgRP neurons are differentially involved in mediating the regional SNA effects of leptin.