CTRP6 in the response to caloric surplus and obesity reversal

Brief Abstract in Lay Terms CTRP6 as a mediator in adaptive and maladaptive response to caloric surplus and in obesity reversal BSF-2017027 Assaf Rudich, M.D., Ph.D., Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University, Beer-Sheva, Israel G. William Wong, Ph.D., Department of Physiology, Johns Hopkins University (School of Medicine), Baltimore, MD, USA This proposal builds on an emerging role of the protein CTRP6, a member of a wider family of secreted factors regulating immune function and metabolism, in obesity. CTRP6 has been shown by Prof. Wong as a novel mediator of metabolic deterioration that accompanies established obesity. In other diseases CTRP6 was proposed to relieve the disease process. In this proposal we joined forces and interests in studying the communication between adipose tissue, the cells that comprise it, the liver, and the bone-marrow (where immune cells are produced) to understand whether and how CTRP6 mediates adaptation to short-term changes in energy supply and in the chronic obese state. We propose to both “deconstruct the system”, by studying the direct effect of CTRP6 on the respective cells in culture, and to study the “reconstructed system” by using both normal mice and mice that are genetically deficient of CTRP6. We will explore a “pre-obese” state by feeding mice a high-calorie containing diet for 2 weeks, and will also assess the early effect after switching obese mice back to normal diet. These studies will help determine how CTRP6, particularly produced by adipose tissue, might be manipulated to achieve beneficial immune-metabolic effects in obese patients with metabolic dysfunction.