The canonical and non-canonical function of β-arrestins in adipose tissue metabolism
Dr. GPCR Ecosystem
Abstract
Obesity, which is characterized by the accumulation of excess fat in adipose tissue, has become a major threat to human health in most parts of the world. Obesity is closely linked to numerous diseases including type 2 diabetes (T2D), cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis. In addition, obesity is a risk factor for a variety of malignancies and neurological diseases. In the past few decades, the global prevalence of obesity has increased considerably. Thus, there is an urgent need for the development of drugs for the treatment of obesity and associated metabolic disorders.
Activation of certain G protein-coupled receptors (GPCRs) in adipose tissue has been reported to have beneficial effects on whole-body glucose homeostasis. GPCR signaling is modulated by proteins of the β-arrestin family (barr1 and barr2), which can terminate GPCR signaling and/or mediate GPCR-independent signaling. Since recent studies have revealed that barr1 and barr2 regulate many important physiological functions, the in vivo roles of β-arrestins have become the focus of intense research. The role of barr1 and barr2 in regulating adipocyte function and whole-body glucose homeostasis remains unexplored. To shed light on this issue, we generated mutant mice that lack barr1 or barr2 (or both barr1 and barr2) selectively in adipocytes. Interestingly, our data support the novel concept that barr2 deficiency promotes beiging of subcutaneous fat and improves whole-body glucose metabolism by regulating the internalization of β3 adrenergic receptors. In contrast, adipocyte-specific deletion of barr1 impaired glucose metabolism, and mechanistic studies confirmed that barr1 regulates the expression of myostatin in brown adipose tissue at the transcription level. These findings raise the possibility that pharmacological manipulation of barr1/barr2 signaling in adipose tissue may prove clinically useful for the treatment of T2D.
About Dr. Sai Prasad Pydi
Dr. Sai Prasad Pydi is an Assistant Professor in the Biological Sciences and Bioengineering (BSBE) department at the Indian Institute of Technology (IIT)-Kanpur. Dr. Pydi's research focuses primarily on the development of GPCR-based remedies for the treatment of obesity and Type 2 Diabetes (T2D) by investigating metabolically significant signaling pathways in immune cells and insulin-sensitive tissues (liver, pancreas, skeletal muscle, adipose tissue, and brain). His team employs knock-out and transgenic mouse models, single-cell transcriptomics, and various cell culture methods to comprehend the significance of immune cell GPCR signaling and their cross-talk with other insulin-sensitive tissues that regulate glucose and lipid metabolism.
Dr. Pydi earned his Ph.D. from the University of Manitoba in Canada, where Prof. Prashen Chelikani introduced him to G protein-coupled receptors (GPCRs). His doctoral research focused on the structural and functional characterization of bitter taste receptors (T2Rs). In 2014, Dr. Pydi joined Dr. Jurgen Wess’s lab at the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) - NIH, USA as a postdoctoral fellow and trained on understanding the physiological role of GPCR signaling and beta-arrestins in diabetes and obesity. Dr. Pydi received multiple awards and fellowships during his doctoral and post-doctoral training. Currently, he is a DBT/Wellcome Trust-India Alliance intermediate fellow.
Dr. Sai Prasad Pydi on the web
