Ruth Loos, Professor - New York, USA
Obesity is a major risk factor for numerous metabolic and cardiovascular complications, leading to type 2 diabetes (T2D), dyslipidemia, hypertension, and cardiovascular disease (CVD). However, not all obese individuals develop complications; about 17-45% of obese individuals remain metabolically healthy (the so-called “metabolically healthy obese”, MHO). Conversely, not all normal-weight individuals are metabolically healthy; an estimated 7-30% of normal-weight individuals show metabolic abnormalities that are typically seen in the obese (the so-called “metabolically obese normal-weight”, MONW).
The physiological mechanisms that determine why some obese individuals are protected, and why some normal weight individuals are at risk, are poorly understood, because clinical studies are often too small and methods to test presumed pathways involved are too invasive. However, identifying the genes that are associated with MHO and MONW provides an alternative strategy to elucidate the pathways and biology involved.
During this research visit, Dr. Ruth Loos from the Icahn School of Medicine at Mount Sinai (New York) will collaborate with Drs. Torben Hansen and Tuomas Kilpeläinen from the Novo Nordisk Foundation Center for Basic Metabolic Research and with Dr. Susanne Mandrup from the University of Southern Denmark.
By systematically screening the genome using a multi-trait discovery approach, they aim to identify genetic loci that increase obesity risk and, at the same time, have protective effects on cardiometabolic traits (representing the MHO), and vice versa, loci that associate with lower obesity risk, yet also with increased cardiometabolic risk (representing the MONW). Genes associated with MHO and MONW holds the promise to elucidate the physiological pathways that link adiposity and its complications in the general population. These insights may point towards new therapeutic targets to impact clinical care. The approaches proposed are innovative and take advantage of the newest methods and most comprehensive datasets currently available, including many of the Danish cohort studies.
This collaboration brings together scientists from Denmark and overseas, consolidates ongoing and initiates new collaborations, connects genetic epidemiologists with molecular biologists and physiologists for translational research and creates opportunities for continued collaborations in the future.