Journal Article

Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates uncoupling protein 1 (Ucp1) expression in white adipose independently of canonical changes in β-adrenergic receptor signaling

Patwari, Parth, Lee, Richard T., Carroll, Shannon H., Zhang, Ellen, LeClair, Katherine B., Cohen, David E., Wang, Bing F., Rahman, Arifeen, Plutzky, Jorge

2017

Overview

Adaptive thermogenesis and cold-induced activation of uncoupling protein 1 (Ucp1) in brown adipose tissue in rodents is well-described and attributed to sympathetic activation of β-adrenergic signaling. The arrestin domain containing protein Arrdc3 is a regulator of obesity in mice and also appears linked to obesity in humans. We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue. Although this increase in expression did not correspond with significant changes in body weight or energy expenditure, adipocyte-specific Arrdc3-null mice had improved glucose tolerance. It was previously hypothesized that Arrdc3 ablation leads to increased β-adrenergic receptor sensitivity; however, in vitro experiments show that Arrdc3-null adipocytes responded to β-adrenergic receptor agonist with decreased Ucp1 levels. Additionally, canonical β-adrenergic receptor signaling was not different in Arrdc3-null adipocytes. These data reveal a role for Arrdc3 in the regulation of Ucp1 expression in adipocytes. However, this adipocyte effect is insufficient to generate the obesity-resistant phenotype of mice with ubiquitous deletion of Arrdc3, indicating a likely role for Arrdc3 in cells other than adipocytes.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Ablation / Activation / Adipocytes / Adipose tissue / Adipose tissue (brown) / Adipose Tissue, White - metabolism / Adrenergic receptors / Animals / Arrestin / Arrestins - genetics / Arrestins - physiology / Biology / Biology and Life Sciences / Body Composition / Body fat / Body weight / Clonal deletion / Endoscopy / Energy expenditure / Gastroenterology / Gene expression / Glucose tolerance / Hepatology / Kinases / Mammals / Medical schools / Medicine and Health Sciences / Mice / Mice, Knockout / Musculoskeletal system / Nervous system / Obesity / Phosphorylation / Proteins / Receptor mechanisms / Receptors, Adrenergic, beta - metabolism / Research and Analysis Methods / Rodents / Signal Transduction / Signaling / Stem cells / Thermogenesis / Uncoupling protein 1 / Uncoupling Protein 1 - metabolism