Leptin modulates the daily rhythmicity of blood glucose.
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.
['Grosbellet|Edith|E|', 'Dumont|Stephanie|S|', 'Schuster-Klein|Carole|C|', 'Guardiola-Lemaitre|Beatrice|B|', 'Pevet|Paul|P|', 'Criscuolo|François|F|', 'Challet|Etienne|E|']
D000818:Animals D001786:Blood Glucose D002940:Circadian Rhythm D007328:Insulin D020738:Leptin D008055:Lipids D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D009765:Obesity
db/db ob/ob glycemia feeding rhythm Circadian clock plasma lipids,