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Leptin receptor deletion from POMC neurons increases susceptibility to high fat diet‐induced obesity (1126.9)
Author(s) -
Bell Balyssa,
Harlan Shan,
Morgan Donald,
Rahmouni Kamal
Publication year - 2014
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.28.1_supplement.1126.9
Subject(s) - proopiomelanocortin , medicine , endocrinology , leptin receptor , leptin , biology , energy homeostasis , hypothalamus , receptor , adipocyte , arcuate nucleus , obesity , adipose tissue
Leptin, an adipocyte derived hormone, acts in the central nervous system (CNS) to regulate energy homeostasis. Neurons in the hypothalamic arcuate nucleus such as proopiomelanocortin (POMC) neurons represent a major target of leptin to regulate metabolism. However, conditional deletion of the leptin receptor (LepR) from POMC neurons has been shown to result in only a mild obesity phenotype while global or CNS LepR knockout mice are severely obese. Here, we examined the susceptibility of mice lacking the LepR in POMC neurons to high fat feeding. Mice missing the LepR specifically in POMC neurons were generated by crossing LepR fl/fl with POMC Cre . LepR fl/fl ‐POMC Cre mice and littermate controls were fed normal chow or high fat diet (HFD, containing 45% fat/kCal) from 4 to12 weeks of age. Consistent with previous reports, on normal chow, LepRb fl/fl ‐POMC Cre mice have a slight, but significantly (P<0.05), elevated body weight (31±1 g) relative to littermate controls (28±1 g). Strikingly, on HFD, LepRb fl/fl ‐POMC Cre mice exhibited an exaggerated increase in body weight (42±1 g) as compared to control littermates (31±1 g, P<0.05). Fat mass was also significantly (P<0.05) increased in HFD fed LepRb fl/fl ‐POMC Cre mice (3.4±0.1g) relative to control mice (1.9±0.2g). Our results provide direct genetic evidence that LepR in POMC neurons is required for normal adaptation against diet‐induced obesity.