title: [Development of nutritional obesity in transgenic mice with an adrenergic receptivity in adipose tissue comparable with that of humans].
abstract: Obesity is characterized by an excessive development of fat mass which is a consequence of increased fat cell size and/or fat cell number. Several hormones and neurotransmitters are regulators of adipose tissue development and metabolism. Among them, catecholamines play a major role by acting through alpha 2- and beta-adrenergic receptors. Stimulation of alpha 2-adrenergic receptors induce inhibition of lipolysis in mature adipocytes as well as preadipocyte proliferation. The antilipolytic effect mediated by alpha 2-adrenergic receptors is in part responsible for the weak lipid mobilization of some fat deposits in humans (subcutaneous fat in particular). Changes in beta- and alpha 2-adrenergic receptors ratio and function have been proposed to explain the lipolytic disturbances described in some obese subjects. Human and rodent adipocytes differ considerably with respect to the balance between beta- and alpha 2-adrenergic receptors. Human adipocytes express mainly alpha 2- but very few beta 3-adrenergic receptors while the reverse is true for rodent adipocytes. Since no suitable animal model was available to study the contribution of alpha 2/beta-adrenergic balance in adipocytes in vivo, we combined gene targeting and transgenic approaches to create a mice with increased alpha 2/beta-adrenergic ratio in adipose tissue. Specifically, we have generated transgenic mice strains on a beta 3-adrenergic receptor knock-out background which express human alpha 2-adrenergic receptors. No particular phenotype was observed in mice maintained in normal diet whereas when fed a high fat diet, transgenic mice increased significantly body weight and fat mass. These results underline the physiologic relevance of the interaction of the presence of alpha 2-adrenergic receptors with a high fat diet in the control of adipose tissue development.
authors.affiliation: Inserm U317, CHU Rangueil, institut Louis Bugnard, bâtiment L3, 31403 Toulouse cedex 4, France.
authors.forename: I
authors.initials: I
authors.lastname: Castan-Laurell
authors.forename: J
authors.initials: J
authors.lastname: Boucher
authors.forename: A
authors.initials: A
authors.lastname: Rey
authors.forename: D
authors.initials: D
authors.lastname: Sibrac
authors.forename: S
authors.initials: S
authors.lastname: Gesta
authors.forename: C
authors.initials: C
authors.lastname: Pagès
authors.forename: D
authors.initials: D
authors.lastname: Daviaud
authors.forename: M F
authors.initials: MF
authors.lastname: Simon
authors.forename: M
authors.initials: M
authors.lastname: Lafontan
authors.forename: J S
authors.initials: JS
authors.lastname: Saulnier-Blachet
authors.forename: P
authors.initials: P
authors.lastname: Valet
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000172:deficiency / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000172:deficiency / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta