PLoS One; co-auth W. Wahli

PLoS One. 2011;6(9):e25565. Epub 2011 Sep 27.

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

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

Division of Endocrinology, Diabetology and Nutrition, Department of Internal
Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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.

PMID: 21980491  [PubMed - in process]

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