title: Leptin modulates the daily rhythmicity of blood glucose.
abstract: Leptin may affect central and/or peripheral timing, in addition to its well-known regulatory effects on metabolism. Here, we investigated whether leptin can impact rhythmicity of blood glucose and lipids. For that purpose, daily variations of blood glucose and lipids were compared between mice lacking functional leptin receptor (db/db) or deficient for leptin (ob/ob) and controls (db/+ and ob/+, respectively). Next, we investigated whether timed treatment with exogenous leptin in ob/ob mice could modulate blood glucose rhythm. Mice with defective leptin signaling (db/db and ob/ob) have the same phase-opposed timing in glycemia (11 and 9 h shift, respectively) compared to respective controls. By contrast, the phase of plasma lipids rhythms (e.g. triglycerides, non-esterified fatty acid - NEFA, high density lipoprotein - HDL, low density lipoprotein - LDL) remained essentially unchanged, whatever the genotype. Daily injections of leptin (1 mg/kg) in ob/ob mice during nighttime or daytime led to 1-2 h phase-advances of blood glucose rhythm and glucose arrhythmicity, respectively. These injections induced additional phase-dependent shifts of feeding rhythm (ranging from 2.6 h phase-delays to 2.6 h advances). The present study reveals a chronomodulatory role of leptin, and highlights that rhythmic leptin can be a determinant of daily variations of blood glucose and food intake, though not for lipids.
authors.affiliation: Regulation of Circadian Clocks Team, Institute of Cellular and Integrative Neurosciences, CNRS, University of Strasbourg , France .
authors.forename: Edith
authors.initials: E
authors.lastname: Grosbellet
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dumont
authors.forename: Carole
authors.initials: C
authors.lastname: Schuster-Klein
authors.forename: Beatrice
authors.initials: B
authors.lastname: Guardiola-Lemaitre
authors.forename: Paul
authors.initials: P
authors.lastname: Pevet
authors.forename: François
authors.initials: F
authors.lastname: Criscuolo
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids
keywords: Circadian clock; db/db; feeding rhythm; glycemia; ob/ob; plasma lipids,