Effects of intracerebroventricular infusion of leptin in obese Zucker rats

• Published in: Obesity research Vol. 5; no. 5; p. 387
• Main Authors: Al-Barazanji, K.A, Buckingham, R.E, Arch, J.R.S, Haynes, A, Mossakowska, D.E, McBay, D.L, Holmes, S.D, McHale, M.T, Wang, X.M, Gloger, I.S
• Format: Journal Article
• Language: English
• Published: United States 01.09.1997
• Subjects: Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - physiopathology; ADIPOSE TISSUES; AMINO ACID SEQUENCES; AMINO ACID SUBSTITUTIONS; ANIMAL PROTEINS; Animals; AZUCAR EN SANGRE; BAISSE DE POIDS; Blood Glucose - metabolism; BLOOD LIPIDS; BLOOD SUGAR; BODY MASS; BODY TEMPERATURE; Body Weight - drug effects; Brain - drug effects; BROWN ADIPOSE TISSUE TEMPERATURE; CHEMICAL COMPOSITION; COMPOSICION QUIMICA; COMPOSITION CHIMIQUE; CORTICOSTERONE; Corticosterone - blood; Eating - drug effects; ENERGIA; ENERGIE; ENERGY; ENERGY EXPENDITURE; Energy Metabolism; FOOD INTAKE; GLUCOCORTICOIDE; GLUCOCORTICOIDES; GLUCOCORTICOIDS; GLUCOSA; GLUCOSE; HEMOLIPIDOS; Infusion Pumps, Implantable; INGESTION DE ALIMENTOS; Insulin - blood; Leptin; LIPIDE SANGUIN; Male; Mice; MUTACION; MUTATION; Obesity - physiopathology; OVERWEIGHT; PRISE ALIMENTAIRE (HOMME); PROTEINAS; PROTEINE; PROTEINS; Proteins - administration & dosage; Proteins - metabolism; Proteins - pharmacology; RAT; RATA; RATS; Rats, Zucker; RECEPTORS; Recombinant Proteins - pharmacology; REDUCCION DEL PESO; SOBREPESO; SUCRE DU SANG; SURPOIDS; TEJIDO ADIPOSO; TEMPERATURA DEL CUERPO; TEMPERATURE CORPORELLE; TISSU ADIPEUX; TRIGLICERIDOS; TRIGLYCERIDE; TRIGLYCERIDES; Triglycerides - blood; WEIGHT REDUCTION
• ISSN: 1071-7323; 1550-8528
• DOI: 10.1002/j.1550-8528.1997.tb00660.x

The obese Zucker rat (OZR) exhibits a missense mutation in the cDNA for the leptin receptor, producing a single amino acid substitution in the extracellular domain of the receptor. A mutation in the leptin receptor gene of the db/db mouse prevents the synthesis of the long splice variant of the receptor. The possibility that the OZR, like the db/db mouse, is refractory to the actions of murine leptin was tested by infusing the protein intracerebroventricularly via a minipump for 7 days. Lean Zucker rats (LZR) infused with leptin acted as positive controls, and other groups of OZR and LZR were infused with vehicle. In LZR, leptin reduced bodyweight and food intake and increased brown adipose tissue (BAT) temperature. Plasma corticosterone increased (61%) in these rats, and plasma triglycerides fell (78%). Leptin treatment improved tolerance to an oral glucose load (16% reduction in the area under the blood glucose curve) while lowering plasma insulin. In OZR, the actions of leptin were blunted. Food intake was slightly, but not significantly, reduced. Although there was a reduction in the rate of increase in body mass, the effect of leptin was about half that seen in LZR. BAT temperature and glucose tolerance were unchanged. In contrast to the elevated plasma corticosterone seen in LZR, leptin reduced the level of this hormone (27%) in OZR. In OZR and LZR treated with leptin, the plasma leptin levels were increased 24-fold and 47-fold, respectively. The results suggest that leptin retains some efficacy in OZR, although these rats are less responsive than LZR.