Author Interviews, Brigham & Women's - Harvard, Nature, Weight Research / 05.05.2020 Interview with: Ronald Kahn, MD Chief Academic Officer, Joslin Diabetes Center Mary K. Iacocca Professor of Medicine Harvard Medical School What is the background for this study? What are the main findings? Response: Adipose tissue is a heterogeneous organ and composed of several cell types, including mature adipocytes, preadipocytes, stem cells, endothelial cells, and various blood cells. Different adipose depots have distinct physiological functions associated with their anatomical location and cell composition. For example, accumulation of intra-abdominal (visceral) white adipose tissue is associated with insulin resistance and metabolic syndrome, whereas accumulation of subcutaneous adipose tissue is not metabolically detrimental and may be even associated with increased insulin sensitivity. Determining the mechanisms for these phenotypic differences could lead to development of novel therapies for diabetes, obesity, and their associated morbidities. A central challenging question in research of metabolic disease is whether disease risk for diabetes and metabolic syndrome is driven by a subset of fat cells that may interact with environmental stresses in disease pathogenesis in a way different from other fat cells. Indeed, previous studies from the Kahn lab have shown different fat cells in a single depot from the mouse may exhibit developmental heterogeneity. In this new study, we attempted to address this question for human white fat using a synergistic application of several methodologies: 1) single cell transcriptional profiling of human white fat during differentiation, 2) analysis of individual clones of white fat cells taken from humans at surgery, 3) novel computer based network analysis and 4) integration of the gene signatures across experimental models. Single-cell RNA sequencing is an ideal technique to profile gene expression of heterogeneous cell populations obtained from a single tissue, including fat tissue. (more…)
Author Interviews, Weight Research / 15.12.2014

Susanne Mandrup Professor, Department of Biochemistry and Molecular Biology Odense M · Interview with: Susanne Mandrup Professor, Department of Biochemistry and Molecular Biology Odense M · Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Mandrup: Obesity affects more than 1 billion adults globally and represents one of the greatest current threats to human health. Paradoxially, the fat tissues in the human body that stores excess calories might hold the key for a future obesity treatment. Most human fat depots are white fat tissues that store energy as fat; however, humans also have small amounts of brown fat, which primarily acts as an effective fat burner for the production of heat. Recent studies have shown that it is possible to “brown” white fat tissues (e.g. by prolonged cold-exposure) leading to an increase in the energy consumption of the body. The challenge is to understand how energy storing white fat cells are reprogrammed into so-called "brite" (brown-in-white) fat cells in the white adipose tissue and thus make adipose tissue burn off excess energy as heat instead of storing it. In this study we have for the first time investigated how the genome of white fat cells is reprogrammed during browning. We stimulated browning in human white adipocytes by a drug used to treat type II diabetes and compared white and "brite" fat cells. This showed that "brite" fat cells have distinct gene programs which, when active, make these cells particularly energy-consuming. Furthermore, we identified an important factor in the browning process - the gene regulatory protein KLF11 (Kruppel Like Factor-11). (more…)