Depressed expression of adipocyte β-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents

Abstract

OBJECTIVE: To determine whether the dramatic reduction in expression and functional activity of the β₃-adrenergic receptor (AR) and β₁AR subtypes originally observed in adipose tissue of the C57BL/6J Lep^ob/ Lep^ob (‘obese’) mouse are general features of all models of obesity, and whether obesity-related differences in βAR subtype expression occur between adipose depots.

DESIGN: Survey of adipose tissue βAR expression from four mouse models of congenital obesity: the ‘obese’ mouse (C57BL/6J Lep^ob/ Lep^ob), the ‘diabetic’ mouse (C57BL/KsJ LepR^db/LepR^db), the ‘tubby’ mouse (C57BL/6J tub/tub) and the ‘fat’ mouse (C57BL/KsJ Cpe^fat/Cpe^fat), and in a model of high-fat diet-induced obesity in C57BL/6J mice.

MEASUREMENTS: Expression of the βAR subtypes was measured by Northern blot hybridization in white and brown adipose depots.

RESULTS: In the severely obese Lep^ob and LepR^db mice, mRNA concentrations of β₃AR and β₁AR in white adipose tissue (WAT) were decreased by >99% and by >70%, respectively. More modest effects on β₃AR expression were observed in brown adipose tissue (BAT, decreased by 20–30%). In less severe forms of obesity, as found in the tubby and carboxypeptidase (Cpe)^fat mice, and in diet-induced obese B6 mice, β₃AR expression was decreased in WAT by up to 90%, with more modest decreases in interscapular BAT (IBAT). Changes in β₁AR mRNA concentrations were more variable. β₂AR mRNA levels did not differ in most cases, with the exception that there was a 3–5-fold increase in BAT for both Lep^oband LepR^db mice.

C0NCLUSIONS: Impaired expression of adipocyte βAR subtypes is a general feature of both genetic and dietary obesity in mice. The degree of obesity is correlated with the extent of loss of β₃AR and β₁AR expression in WAT. The distinct endocrine abnormalities associated with these obesity models may be responsible for the degree of impaired adipocyte βAR expression.