Adipocyte Biology: How does Obesity cause Diabetes?
Adipose tissue in human subjects has the remarkable and unique property of being able to expand to 100 pounds or more during the development of obesity. This expansion involves hundreds of fascinating pathways that are coordinated to store fat within adipocytes. These include activation of genomic networks through chromatin remodeling, epigenetic regulation of gene expression, cell proliferation and differentiation, cell signaling and trafficking, infiltration of immune cells into adipose tissue and crosstalk between adipocytes and neurons. Hidden within these various mechanisms of adipose expansion is the mystery of why some obese humans develop type 2 diabetes while others at the same weight do not. This is a mystery of enormous importance since most people in the US are overweight or obese, and the incidence of diabetes is a staggering 9% of the population.
Investigators in the Program in Molecular Medicine are tackling the mechanisms in metabolic tissues that go awry in obesity and lead to the onset of diabetes. Recent advances include the discovery of how to culture unique human adipocytes that are specialized to burn fat rather than store it, as well as discoveries of signaling pathways that activate these fat burning cells. These and other findings have provided strategies for the prevention and treatment of obesity and type 2 diabetes.
Sphingolipids are structural components of membranes and also bioactive lipids regulating growth, differentiation, apoptosis, intracellular trafficking and membrane turnover among other cellular processes. We use a combined genetic, molecular and biochemical approach to elucidate physiological functions for these lipids and to understand mechanisms that control sphingolipid homeostasis. (Acharya profile)
Our laboratory has two main interests. One is the mechanism by which phosphoinositides control signal transduction and membrane trafficking in the endosomal system. The second more recent interest is centered on the question of how cells and organisms sense, generate, utilize and store energy. Energy metabolism is essential to life, and many diseases are associated with altered metabolism, including cancer and diabetes. We hope our research will lead to a better understanding and treatment of human diseases. (Corvera profile)
Our laboratory group is dedicated to the discovery of molecular mechanisms whereby insulin signaling regulates energy homeostasis. This quest includes RNAi screens, digital imaging and TIRF microscopy, phenotyping mice with gene knockouts and analysis of human adipose tissues. We hope to translate our findings to the prevention and treatment of type 2 diabetes. (Czech profile)
The cJun NH2-terminal kinase (JNK) signal transduction pathway is implicated in several stress-related disease processes including cancer, diabetes, inflammation, and stroke. Our hope is that drugs targeting the JNK pathway may be useful for the treatment of these diseases. The goal of this laboratory is to understand the molecular processes that are engaged by JNK in both health and disease. (Davis profile)
Our laboratory investigates the pathogenesis of type 1 diabetes, how to prevent it, and how to reverse it through islet transplantation. We use mouse and rat models of type 1 diabetes, and are building mice with human immune systems that permit the direct study of human disease without putting patients at risk. (Greiner profile)
We study the molecular basis of growth and how defects in growth regulatory pathways contribute to cancer, metabolic disorders, and aging. In particular we are trying to understand how cells simultaneously sense nutrient availability, energy levels, and growth factors and use this information to control cell metabolism, cell growth, and cell proliferation. Our approach is multidisciplinary and employs genetic, cell biological, and biochemical strategies using mice, stem cells, and established mammalian cell lines. (Guertin profile)
Our research investigates obesity, diabetes and its complications using elegant metabolic procedures and transgenic mouse models of altered metabolism. Our NIH-funded projects examine the role of inflammation in insulin resistance and cardiovascular diseases. The goal of our research is to understand how obesity causes diabetes and to find its cure. (Kim profile)
We aim to understand how regulatory networks control animal development, function, and homeostasis; and how dysfunctional networks affect or cause diseases like diabetes, obesity and cancer. We use a combination of experimental and computational systems biology methods to map, characterize and manipulate regulatory networks, most notably in the nematode C. elegans. (Walhout profile)
Using C. elegans and mammalian models, we study how lipid homeostasis is affected by genetics or diet and how transcriptional control of methyl donor supply may affect cellular processes such as epigenetics. We also examine links between metabolism and cellular function potentially contributing to human metabolic disorders. (Walker profile)
Our focus in the lab is to dissect the functional roles of nuclear receptor PPARs and their co-regulators in glucose and fatty acid metabolism and metabolic diseases, and to understand their molecular mechanisms of action. A combination of tools, including molecular biology, mouse genetics, physiology and genomics, will be employed. (Wang profile)
Adjunct Professor of Molecular Medicine, UMMS, is presently Professor of Clinical Integrative Physiology and Head of the Section of Integrative Physiology at the Department of Molecular Medicine and Surgery and the Department of Physiology and Pharmacology at Karolinska Institutet, Stockholm Sweden, where she is Director of the The Strategic Research Programme in Diabetes. She is also Professor of Integrative Physiology at University of Copenhagen, where she is a Scientific Director at the Marie Krogh Center for Metabolic Research, Copenhagen Denmark. (Zierath profile)