Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats

Autor: Anne-Lise Bussier, Walter Wahli, Jean-Jacques Legros, Lucie Bourgoin, Michelangelo Foti, Stefania Petrosino, Vincent Geenen, Fabiana Piscitelli, Vincenzo Di Marzo, Françoise Rohner-Jeanrenaud, Christelle Veyrat-Durebex, Aurélie Caillon, Nicolas Deblon
Rok vydání: 2011
Předmět:
Male
PPAR alpha/deficiency/genetics/metabolism
Anatomy and Physiology
Oxytocin/administration & dosage/biosynthesis/blood/pharmacology
medicine.medical_treatment
Adipose tissue
lcsh:Medicine
Oleic Acids
Oxytocin
Biochemistry
Oleoylethanolamide
chemistry.chemical_compound
Gene Knockout Techniques
Mice
0302 clinical medicine
Endocrinology
Lactation
lcsh:Science
2. Zero hunger
ddc:616
0303 health sciences
Multidisciplinary
Chemistry
Lipids
Obesity/drug therapy/etiology/metabolism/physiopathology
medicine.anatomical_structure
Anti-Obesity Agents/administration & dosage/blood/metabolism/pharmacology
Adipose Tissue
Medicine
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Research Article
medicine.medical_specialty
030209 endocrinology & metabolism
Endocrine System
03 medical and health sciences
Insulin resistance
Oleic Acids/biosynthesis/metabolism
Diet/adverse effects
Internal medicine
medicine
Adipose Tissue/drug effects/metabolism
Lipolysis
Animals
PPAR alpha
Body Weight/drug effects
Obesity
ddc:612
Biology
030304 developmental biology
Nutrition
Dose-Response Relationship
Drug
Endocrine Physiology
Insulin
Body Weight
lcsh:R
medicine.disease
Lipid Metabolism
Hormones
Diet
Rats
lcsh:Q
Anti-Obesity Agents
Insulin Resistance
Diet-induced obese
Endocannabinoids
Zdroj: PloS one
PLoS One, vol. 6, no. 9, pp. e25565
PLoS ONE, Vol 6, Iss 9, p e25565 (2011)
PLoS ONE
PLOS ONE, Vol. 6, No 9 (2011) P. e25565
PLoS One
PloS one 6 (2011): 25565.
info:cnr-pdr/source/autori:Deblon N, Veyrat-Durebex C, Bourgoin L, Caillon A, Bussier AL, Petrosino S, Piscitelli F, Legros JJ, Geenen V, Foti M, Wahli W, Di Marzo V, Rohner-Jeanrenaud F./titolo:Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats./doi:/rivista:PloS one/anno:2011/pagina_da:25565/pagina_a:/intervallo_pagine:25565/volume:6
ISSN: 1932-6203
Popis: Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.
Databáze: OpenAIRE
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