Effects of intravenously infused leptin on insulin sensitivity and on the expression of uncoupling proteins in brown adipose tissue.
Centrally administered leptin has been shown to increase insulin-stimulated glucose utilization and to favor the expression of uncoupling proteins (UCPs). To study if leptin also has direct peripherally mediated effects on these processes, this hormone (1 mg/day) or its vehicle was infused i.v. for 4 days to lean rats and insulin-stimulated glucose utilization in skeletal muscle and adipose tissue as well as the expression of UCP messenger RNAs (mRNAs) in brown adipose tissue were measured. I.v. leptin administration resulted in decreases in food intake (31%), body weight gain, and plasma insulin levels (45%), in increases in overall (23%) as well as brown adipose tissue and muscle glucose utilization, and in decreases in white adipose tissue glucose uptake. Most of these changes were mimicked, in control rats, by giving them the same amount of food as that consumed by the leptin-infused group (pair-feeding). I.v. leptin infusion also favored the expression of UCPs in brown adipose tissue, either by increasing their expression or preventing the fall occurring during the pair-feeding regimen. Relative UCP expression levels were 100, 104, and 33 for UCP1, 100, 191, and 125 for UCP2 and 100, 107, and 29 for UCP3 in ad libitum fed control rats, in leptin-treated rats and in pair-fed control rats, respectively. These results suggest that the overall effect of leptin on glucose utilization and on the expression of UCPs may be mediated through central mechanism.
Rouru
J
J
Laboratoires de Recherches Métaboliques, Hôpital Cantonal Universitaire de Genève, Switzerland. juha.rouru@orion.fi
Cusin
I
I
Zakrzewska
K E
KE
Jeanrenaud
B
B
Rohner-Jeanrenaud
F
F
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007473:Ion Channels; D020738:Leptin; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013851:Thinness; D014158:Transcription, Genetic / Q000187:drug effects; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D015430:Weight Gain
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C000604373:Ucp1 protein, rat; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D005947:Glucose