Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats.
Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.
Dept. of Medicine, University of Washington at South Lake Union, 815 Mercer Street, Seattle, WA 98109, USA. gjmorton@u.washington.edu
Gregory J
GJ
Morton
Brendan S
BS
Thatcher
Roger D
RD
Reidelberger
Kayoko
K
Ogimoto
Tami
T
Wolden-Hanson
Denis G
DG
Baskin
Michael W
MW
Schwartz
James E
JE
Blevins
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000627:therapeutic use*; D031608:Area Postrema / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D020738:Leptin / Q000097:blood; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D010121:Oxytocin / Q000008:administration & dosage / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D054411:Receptors, Leptin / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015431:Weight Loss / Q000187:drug effects*
D001067:Appetite Depressants; D004041:Dietary Fats; D020738:Leptin; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D010121:Oxytocin