Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes.
Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15-16 week old obese and diabeticdb/dbmice using liquid chromatography-tandem mass spectrometry. Leandb/+served as controls.Db/dbmice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold indb/dbmice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher indb/dbmice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals,Cyp11b2,Cyp11b1,Cyp21a1,Hsd3b1,Cyp11a1, andStARwere all significantly increased indb/dbmice compared withdb/+controls. In adipose tissue, noCyp11b2orCyp11b1transcripts were detected and no differences inCyp21a1,Hsd3b1,Cyp11a1, orStARexpression were found betweendb/+anddb/dbmice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in thedb/dbmodel of obesity and type 2 diabetes.
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Anja
A
Hofmann
Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Mirko
M
Peitzsch
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Coy
C
Brunssen
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Jennifer
J
Mittag
Department of Cardiac Surgery, Herzzentrum Dresden, Medical Faculty Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Annett
A
Jannasch
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Annika
A
Frenzel
Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
Nicholas
N
Brown
Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
Steven M
SM
Weldon
Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Graeme
G
Eisenhofer
Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Stefan R
SR
Bornstein
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Henning
H
Morawietz
D000305:Adrenal Cortex Hormones / Q000097:blood / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003900:Desoxycorticosterone / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011374:Progesterone / Q000097:blood / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D012739:Gonadal Steroid Hormones; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D003345:Corticosterone