Titre du document / Document title

Sibutramine-dependent brown fat activation in rats: an immunohistochemical study

Auteur(s) / Author(s)

GIORDANO A. ⁽¹⁾ ; CENTEMERI C. ⁽²⁾ ; ZINGARETTI M. C. ⁽¹⁾ ; CINTI S. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Institute of Normal Human Morphology-Anatomy, Faculty of Medicine, University of Ancona, Ancona, ITALIE
⁽²⁾ Knoll Farmaceutici Spa, Muggiò Milano, ITALIE

Résumé / Abstract

OBJECTIVES: To evaluate morphological aspects and immunohistochemical markers of brown adipose tissue (BAT) activation following chronic treatment with sibutramine, a novel anti-obesity drug which increases thermogenesis and energy expenditure in mammals, and to establish whether chronic sibutramine treatment induces recruitment of BAT in white adipose tissue (WAT) depots. DESIGN: Adult rats were administered 7 mg/kg/day oral sibutramine for 4 weeks. Body weight was monitored daily. At the end of the 4 weeks rats were perfused with buffered paraformaldehyde solution; interscapular BAT and retroperitoneal and epididymal WAT were carefully dissected for weight and volume measurements and processed for light microscopic studies and immunohistochemistry on paraffin-embedded sections. Where possible, semiquantitative morphometric analyses were performed. RESULTS: Chronic sibutramine treatment determined a significant (about 8%) reduction in body weight. Compared with controls, sibutramine-treated rats showed: (1 ) interscapular brown adipocytes staining more intensely for uncoupling protein 1 (UCP1), the thermogenic mitochondrial protein; (2) a significantly larger number (about 45%) of brown adipocyte nuclei positive for peroxisome proliferator-activated receptor γ, the transcription factor driving UCP1 expression; (3) surprisingly, a significant reduction (about 30%) in BAT parenchymal noradrenergic nerve staining; and (4) a significant weight and volume reduction of WAT depots, but no significant signs of transdifferentiation of white into brown adipocytes. CONCLUSION: This study confirms the ability of sibutramine to induce weight loss by selective and sustained activation of BAT in rodents without recruitment of brown fat in WAT depots. The parallel findings of a high level of brown adipocyte activation and low parenchymal noradrenergic innervation are discussed and a possible direct effect of sibutramine and/or its active metabolites on peripheral BAT sympathetic nerve terminals is hypothesized.

Revue / Journal Title

International journal of obesity   ISSN 0307-0565   CODEN IJOBDP 

Source / Source

2002, vol. 26, n^o3, pp. 354-360 (60 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing, Basingstoke, ROYAUME-UNI  (1977) (Revue)

Mots-clés anglais / English Keywords

Nutrition disorder ; Vertebrata ; Mammalia ; Rodentia ; Human ; Energetic cost ; Thermogenesis ; Treatment ; Nutritional status ; Chronic ; Brown adipose tissue ; Rat ; Activation ; Fat ; Oral administration ; Adult ; White adipose tissue ; Animal ; Peripheral nerve ; Retroperitoneal ; Immunohistochemistry ; Sibutramine ; Obesity ;

Mots-clés français / French Keywords

Trouble nutrition ; Vertebrata ; Mammalia ; Rodentia ; Homme ; Dépense énergétique ; Thermogenèse ; Traitement ; Etat nutritionnel ; Chronique ; Tissu adipeux brun ; Rat ; Activation ; Matière grasse ; Voie orale ; Adulte ; Tissu adipeux blanc ; Animal ; Nerf périphérique ; Rétropéritonéal ; Immunohistochimie ; Sibutramine ; Obésité ;

Mots-clés espagnols / Spanish Keywords

Trastorno nutricíon ; Vertebrata ; Mammalia ; Rodentia ; Hombre ; Costo energético ; Termogénesis ; Tratamiento ; Estado nutricional ; Crónico ; Tejido adiposo cafe ; Rata ; Activación ; Materia grasa ; Vía oral ; Adulto ; Tejido adiposo blanco ; Animal ; Nervio periférico ; Retroperitoneal ; Inmunohistoquímica ; Sibutramina ; Obesidad ;

Localisation / Location

INIST-CNRS, Cote INIST : 18243, 35400010279397.0080