Chronic β3 adrenergic stimulation induced remodeling of white adipose tissue in mice

Obesity and associated co‐morbidities are major health concerns. Here we define how a potential pharmacological treatment for obesity ( in vivo chronic stimulation of β3‐adrenergic receptors with CL 316,243) affects remodeling of intra‐abdominal fat and specific serum markers closely related to obesity‐associated co‐morbidities. Male C57Bl/6 mice (n=8/group) were studied during 14 days of either no intervention (controls) or CL infusion (1mg/kg/day via Alza pump) with epididymal fat pads collected at sacrifice. CL treatment had no effect on food intake or body weight but decreased epididymal fat pad mass from 250±29 to 121±19 mg (p<0.01). While CL treatment did not change the protein concentration of whole adipose tissue or the non‐adipocyte cell fraction, it increased protein concentration in the adipocyte fraction > 4‐fold (0.2±0.04 to 0.9±0.09 mg/ml, p<0.01). CL treatment decreased blood glucose from 202±10 to 144±10 mg/dl (p<0.01) and serum leptin from 2.0±0.2 to 1.3±0.2 ng/ml (p<0.01). The cardioprotective adipokine adiponectin was increased from 6.2±0.3 to 8.3±0.3 μg/ml (p<0.01) by CL treatment. We conclude that the favorable serum changes induced by β3‐adrenergic stimulation are not dependent on decreased body weight but instead are likely linked to a remodeling of adipose tissue involving primarily the adipocytes.