title: Leptin-dependent control of glucose balance and locomotor activity by POMC neurons.
abstract: Leptin plays a pivotal role in regulation of energy balance. Via unknown central pathways, leptin also affects peripheral glucose homeostasis and locomotor activity. We hypothesized that, specifically, pro-opiomelanocortin (POMC) neurons mediate those actions. To examine this possibility, we applied Cre-Lox technology to express leptin receptors (ObRb) exclusively in POMC neurons of the morbidly obese, profoundly diabetic, and severely hypoactive leptin receptor-deficient Lepr(db/db) mice. Here, we show that expression of ObRb only in POMC neurons leads to a marked decrease in energy intake and a modest reduction in body weight in Lepr(db/db) mice. Remarkably, blood glucose levels are entirely normalized. This normalization occurs independently of changes in food intake and body weight. In addition, physical activity is greatly increased despite profound obesity. Our results suggest that leptin signaling exclusively in POMC neurons is sufficient to stimulate locomotion and prevent diabetes in the severely hypoactive and hyperglycemic obese Lepr(db/db) mice.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Huo
authors.forename: Kevin
authors.initials: K
authors.lastname: Gamber
authors.forename: Sarah
authors.initials: S
authors.lastname: Greeley
authors.forename: Jose
authors.initials: J
authors.lastname: Silva
authors.forename: Nicholas
authors.initials: N
authors.lastname: Huntoon
authors.forename: Xing-Hong
authors.initials: XH
authors.lastname: Leng
authors.forename: Christian
authors.initials: C
authors.lastname: Bjørbaek
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004435:Eating; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D020738:Leptin; D054411:Receptors, Leptin; D011333:Pro-Opiomelanocortin