Human alpha 2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements.
Catecholamines regulate white adipose tissue function and development by acting through beta- and alpha2-adrenergic receptors (ARs). Human adipocytes express mainly alpha 2A- but few or no beta 3-ARs while the reverse is true for rodent adipocytes. Our aim was to generate a mouse model with a human-like alpha2/beta-adrenergic balance in adipose tissue by creating transgenic mice harbouring the human alpha 2A-AR gene under the control of its own regulatory elements in a combined mouse beta 3-AR-/- and human beta 3-AR+/+ background. Transgenic mice exhibit functional human alpha 2A-ARs only in white fat cells. Interestingly, as in humans, subcutaneous adipocytes expressed higher levels of alpha2-AR than perigonadal fat cells, which are associated with a better antilipolytic response to epinephrine. High-fat-diet-induced obesity was observed in transgenic mice in the absence of fat cell size modifications. In addition, analysis of gene expression related to lipid metabolism in isolated adipocytes suggested reduced lipid mobilization and no changes in lipid storage capacity of transgenic mice fed a high-fat diet. Finally, the development of adipose tissue in these mice was not associated with significant modifications of glucose and insulin blood levels. Thus, these transgenic mice constitute an original model of diet-induced obesity for in vivo physiological and pharmacological studies with respect to the alpha2/beta-AR balance in adipose tissue.
Boucher
J
J
INSERM U317, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse cedex 4, France.
Castan-Laurell
I
I
Le Lay
S
S
Grujic
D
D
Sibrac
D
D
Krief
S
S
Lafontan
M
M
Lowell
B B
BB
Dugail
I
I
Saulnier-Blache
J-S
JS
Valet
P
P
D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D001835:Body Weight; D048429:Cell Size; D004041:Dietary Fats / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D014018:Tissue Distribution
C547768:ADRA2A protein, human; C547769:Adra2a protein, mouse; D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta