Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation.
Intra-abdominal fat accumulation is involved in development of the metabolic syndrome, which is associated with insulin and leptin resistance. We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance. UCP1 expression in Epi improved glucose tolerance and decreased food intake in both diet-induced and genetically obese mouse models. In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels. Thus, hypophagia induction requires a leptin signal, while the improved insulin sensitivity appears to be leptin independent. In wild-type mice, local-nerve dissection in the epididymis or pharmacological afferent blockade blunted the decrease in food intake, suggesting that afferent-nerve signals from intra-abdominal fat tissue regulate food intake by modulating hypothalamic leptin sensitivity. These novel signals are potential therapeutic targets for the metabolic syndrome.
Yamada
Tetsuya
T
Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Katagiri
Hideki
H
Ishigaki
Yasushi
Y
Ogihara
Takehide
T
Imai
Junta
J
Uno
Kenji
K
Hasegawa
Yutaka
Y
Gao
Junhong
J
Ishihara
Hisamitsu
H
Niijima
Akira
A
Mano
Hiroyuki
H
Aburatani
Hiroyuki
H
Asano
Tomoichiro
T
Oka
Yoshitomo
Y
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004822:Epididymis / Q000166:cytology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D005947:Glucose