title: Leptin action via LepR-b Tyr1077 contributes to the control of energy balance and female reproduction.
abstract: Leptin action in the brain signals the repletion of adipose energy stores, suppressing feeding and permitting energy expenditure on a variety of processes, including reproduction. Leptin binding to its receptor (LepR-b) promotes the tyrosine phosphorylation of three sites on LepR-b, each of which mediates distinct downstream signals. While the signals mediated by LepR-b Tyr1138 and Tyr985 control important aspects of energy homeostasis and LepR-b signal attenuation, respectively, the role of the remaining LepR-b phosphorylation site (Tyr1077) in leptin action has not been studied. To examine the function of Tyr1077, we generated a "knock-in" mouse model expressing LepR-b (F1077), which is mutant for LepR-b Tyr1077. Mice expressing LepR-b (F1077) demonstrate modestly increased body weight and adiposity. Furthermore, females display impairments in estrous cycling. Our results suggest that signaling by LepR-b Tyr1077 plays a modest role in the control of metabolism by leptin, and is an important link between body adiposity and the reproductive axis.
authors.affiliation: Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
authors.forename: Christa M
authors.initials: CM
authors.lastname: Patterson
authors.forename: Eneida C
authors.initials: EC
authors.lastname: Villanueva
authors.forename: Megan
authors.initials: M
authors.lastname: Greenwald-Yarnell
authors.forename: Michael
authors.initials: M
authors.lastname: Rajala
authors.forename: Ian E
authors.initials: IE
authors.lastname: Gonzalez
authors.forename: Natinder
authors.initials: N
authors.lastname: Saini
authors.forename: Justin
authors.initials: J
authors.lastname: Jones
authors.forename: Martin G
authors.initials: MG
authors.lastname: Myers
keywords: ARC, arcuate nucleus; AgRP, agouti-related peptide; BAT, brown adipose tissue; Estrus; HD, high-fat diet; IVGTT, intravenous glucose tolerance test; Kiss, kisspeptin; LepR-b, leptin receptor; Leptin; NC, normal chow; NPY, neuropeptide Y; Obesity; PMv, ventral premammilary nucleus; POMC, proopiomelanocortin; Reproduction; STAT5; STAT5, signal transducer and activator of transcription-5; TAC2, tachykinin-2; Tyrosine phosphorylation; WAT, white adipose tissue
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