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Special issue on lipotoxicity
Biochimica et Biophysica Acta 1801 (2010) 207–208
Contents lists available at ScienceDirect
Biochimica et Biophysica Acta j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / b b a l i p
Editorial
Special issue on lipotoxicity
It was sometime in March 2009 when our colleague Fritz Spener first proposed a special issue of BBA Molecular and Cell Biology of Lipids focused on the concept of lipotoxicity and its relevance as an integrative pathogenic mechanism of the metabolic syndrome. Although we might have hesitated a little initially, this did not last long as we realised that: a) ours would be a unique, high quality publication addressing the topic in depth and globally; b) this is an important area of research with enormous implications for metabolic disease and, in our opinion, its relevance is underestimated and relatively unknown among both the biomedical community and general public; and c) the great opportunities offered by new technologies and experimental models to understand the role of lipotoxicity in common metabolic diseases makes this a very timely issue. And also, of course, we expected strong support from the “lipotoxic community”. Certainly we have not been disappointed. In fact our colleagues have provided enormous support and their generosity has made this issue viable. Our only regret is that we have not been able to involve as many of the key experts as we wanted due to space constrains and the time scale of the project, and we hope this will not be the cause of any lost friendships! The issue is organised into several broad areas, starting with the definition and the technological approaches (lipidomics, systems biology and metabolomics) and models (flies and yeast) used to study lipotoxicity. The second group of reviews addresses the role and specific characteristics of lipotoxicity in organs such as adipose tissue, beta cells, muscle, liver, heart, macrophages, hypothalamus and the CNS, and their involvement in the pathogenesis of the metabolic syndrome. We then focus on how interventions and treatments that improve the metabolic syndrome may do so through their effects on lipotoxicity. These include reviews on nutrition, life-style, exercise and pharmacological approaches. The next section includes reviews that expand the concept of lipotoxicity to areas such as cancer and neurodegenerative diseases, which are becoming associated with the metabolic syndrome. Contrary to other issues in this series we conclude with an epidemiological review. There is a reason for this: as the issue developed, I convinced my colleague Sorensen to think about lipotoxicity from an epidemiological perspective, and I think the “lipotoxic community” managed to convince him that there is in fact a case to be made for redefining obesity from a lipotoxic point of view. All together we are very satisfied with the outcome of this editorial experience and hope our readers appreciate the quality of each contribution and the generosity of the insights they contain. We are delighted that authors have gone much further than just summarising available information, rather they have provided original points of view and stimulating information that will guide future research. Also
1388-1981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbalip.2009.12.010
they have been excellent reviewers of the other contributions. We are very thankful to all of them for their help in putting together this issue. Other people to acknowledge are members of our laboratories, my personal assistant Sophie Gough for her editorial assistance, and the editorial team from BBA, particularly Charity Houston for her excellent assistance. Finally we would like to thank Fritz Spener and our colleague Rudy Zechner for their support while crafting this issue. Dr Vidal-Puig obtained his medical degree from Valencia Medical School (Spain) before training in clinical endocrinology at Granada Medical School (Spain), where he obtained his PhD based on clinical and physiological studies of the relationship between insulin resistance and hyperandrogenism. The award of the Paul Dudley White Fellowship from the American Heart Association funded post-doctoral training at Harvard University, supporting his work with Dr David Moller and Prof Jeffrey Flier at the Beth Israel Hospital. Having published several key papers on the genetics and expression of PPARg in human disease states and been appointed Instructor in Medicine at Harvard, Dr Vidal-Puig further broadened his scientific horizons with experience in mouse transgenesis and knockout techniques in Prof Brad Lowell's group. In 2000 he moved to the University of Cambridge to establish his own laboratory and embark on the development of a programme based on genetically modified mouse models of metabolic diseases. Dr Vidal-Puig is currently the Professor of Molecular Nutrition and Metabolism at Cambridge University and Honorary Consultant in Metabolic Medicine at Addenbrooke's Hospital, Cambridge. He is Deputy Director of the MRC Centre for Obesity and Related Diseases and Director of the Cambridge Phenomics Centre, a state-of-the-art centre that applies multidisciplinary approaches to murine phenotyping. His programme of research focuses on the molecular mechanisms of lipid-induced insulin resistance and on developing strategies to prevent the deleterious effects of lipids, specifically by modulating fatty acid oxidation and thermogenic mechanisms.
Dr. Unger is the Touchstone/West Distinguished Chair in Diabetes Research and Professor of Internal Medicine at the University of Texas Southwestern Medical Center, and at the Dallas Veterans Affairs Medical Center. Dr. Unger’s early contributions established the hormonal status of glucagon and elucidated its physiologic role and its pathophysiologic impact in diabetes, thanks to his development in 1959 of a glucagon radioimmunoassay and the development of the insulin RIA of Yalow and Berson. The Unger lab was the first to study the bihormonal interplay of the islet hormones in diabetes and other metabolic states. These contributions earned him the highest research awards of the American Diabetes Association, Endocrine Society, the European Association for the Study of Diabetes, and the Juvenile Diabetes Research Foundation, and led to his election to the National Academy of Sciences in 1986. He holds Doctor Honoris Causa degrees from the Universities of Liege and Geneva. In collaboration with Dr. J. Denis McGarry, Dr. Unger discovered that ectopic lipid deposition or “lipotoxicity” is the link between obesity and type 2 diabetes and other components of metabolic syndrome, and that the resulting lipid-induced cell death or “lipoapoptosis” can be completely prevented by enhanced oxidation of the ectopic fatty acids.
208
Editorial
During the past two years, Dr. Unger’s research has shifted to type 1 diabetes. He has reported on a novel method for extending the survival of islet transplanted into the livers of type 1 diabetic recipients. These studies led to the discovery that leptin, which prevented the loss of function of islet transplants, also normalized the blood glucose levels in type 1 diabetic animals that had never received islets. Thus, leptin normalizes glucose in type 1 diabetes–the first such substance to do so since the discovery of insulin in 1922. After completing the animal experiments, Dr. Unger plans to apply for permission to begin human studies, in the hope that leptin treatment can replace insulin therapy and improve the quality of life for type 1 patients.
A. Vidal-Puig University of Cambridge Metabolic Research Laboratories, Cambridge, UK E-mail address: [email protected]. Corresponding author. Roger H. Unger The University of Texas Southwestern Medical Center, Dallas, USA E-mail address: [email protected]. Corresponding author. Corresponding author.The University of Texas Southwestern Medical Center, Dallas, USA
Contents lists available at ScienceDirect
Biochimica et Biophysica Acta j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / b b a l i p
Editorial
Special issue on lipotoxicity
It was sometime in March 2009 when our colleague Fritz Spener first proposed a special issue of BBA Molecular and Cell Biology of Lipids focused on the concept of lipotoxicity and its relevance as an integrative pathogenic mechanism of the metabolic syndrome. Although we might have hesitated a little initially, this did not last long as we realised that: a) ours would be a unique, high quality publication addressing the topic in depth and globally; b) this is an important area of research with enormous implications for metabolic disease and, in our opinion, its relevance is underestimated and relatively unknown among both the biomedical community and general public; and c) the great opportunities offered by new technologies and experimental models to understand the role of lipotoxicity in common metabolic diseases makes this a very timely issue. And also, of course, we expected strong support from the “lipotoxic community”. Certainly we have not been disappointed. In fact our colleagues have provided enormous support and their generosity has made this issue viable. Our only regret is that we have not been able to involve as many of the key experts as we wanted due to space constrains and the time scale of the project, and we hope this will not be the cause of any lost friendships! The issue is organised into several broad areas, starting with the definition and the technological approaches (lipidomics, systems biology and metabolomics) and models (flies and yeast) used to study lipotoxicity. The second group of reviews addresses the role and specific characteristics of lipotoxicity in organs such as adipose tissue, beta cells, muscle, liver, heart, macrophages, hypothalamus and the CNS, and their involvement in the pathogenesis of the metabolic syndrome. We then focus on how interventions and treatments that improve the metabolic syndrome may do so through their effects on lipotoxicity. These include reviews on nutrition, life-style, exercise and pharmacological approaches. The next section includes reviews that expand the concept of lipotoxicity to areas such as cancer and neurodegenerative diseases, which are becoming associated with the metabolic syndrome. Contrary to other issues in this series we conclude with an epidemiological review. There is a reason for this: as the issue developed, I convinced my colleague Sorensen to think about lipotoxicity from an epidemiological perspective, and I think the “lipotoxic community” managed to convince him that there is in fact a case to be made for redefining obesity from a lipotoxic point of view. All together we are very satisfied with the outcome of this editorial experience and hope our readers appreciate the quality of each contribution and the generosity of the insights they contain. We are delighted that authors have gone much further than just summarising available information, rather they have provided original points of view and stimulating information that will guide future research. Also
1388-1981/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbalip.2009.12.010
they have been excellent reviewers of the other contributions. We are very thankful to all of them for their help in putting together this issue. Other people to acknowledge are members of our laboratories, my personal assistant Sophie Gough for her editorial assistance, and the editorial team from BBA, particularly Charity Houston for her excellent assistance. Finally we would like to thank Fritz Spener and our colleague Rudy Zechner for their support while crafting this issue. Dr Vidal-Puig obtained his medical degree from Valencia Medical School (Spain) before training in clinical endocrinology at Granada Medical School (Spain), where he obtained his PhD based on clinical and physiological studies of the relationship between insulin resistance and hyperandrogenism. The award of the Paul Dudley White Fellowship from the American Heart Association funded post-doctoral training at Harvard University, supporting his work with Dr David Moller and Prof Jeffrey Flier at the Beth Israel Hospital. Having published several key papers on the genetics and expression of PPARg in human disease states and been appointed Instructor in Medicine at Harvard, Dr Vidal-Puig further broadened his scientific horizons with experience in mouse transgenesis and knockout techniques in Prof Brad Lowell's group. In 2000 he moved to the University of Cambridge to establish his own laboratory and embark on the development of a programme based on genetically modified mouse models of metabolic diseases. Dr Vidal-Puig is currently the Professor of Molecular Nutrition and Metabolism at Cambridge University and Honorary Consultant in Metabolic Medicine at Addenbrooke's Hospital, Cambridge. He is Deputy Director of the MRC Centre for Obesity and Related Diseases and Director of the Cambridge Phenomics Centre, a state-of-the-art centre that applies multidisciplinary approaches to murine phenotyping. His programme of research focuses on the molecular mechanisms of lipid-induced insulin resistance and on developing strategies to prevent the deleterious effects of lipids, specifically by modulating fatty acid oxidation and thermogenic mechanisms.
Dr. Unger is the Touchstone/West Distinguished Chair in Diabetes Research and Professor of Internal Medicine at the University of Texas Southwestern Medical Center, and at the Dallas Veterans Affairs Medical Center. Dr. Unger’s early contributions established the hormonal status of glucagon and elucidated its physiologic role and its pathophysiologic impact in diabetes, thanks to his development in 1959 of a glucagon radioimmunoassay and the development of the insulin RIA of Yalow and Berson. The Unger lab was the first to study the bihormonal interplay of the islet hormones in diabetes and other metabolic states. These contributions earned him the highest research awards of the American Diabetes Association, Endocrine Society, the European Association for the Study of Diabetes, and the Juvenile Diabetes Research Foundation, and led to his election to the National Academy of Sciences in 1986. He holds Doctor Honoris Causa degrees from the Universities of Liege and Geneva. In collaboration with Dr. J. Denis McGarry, Dr. Unger discovered that ectopic lipid deposition or “lipotoxicity” is the link between obesity and type 2 diabetes and other components of metabolic syndrome, and that the resulting lipid-induced cell death or “lipoapoptosis” can be completely prevented by enhanced oxidation of the ectopic fatty acids.
208
Editorial
During the past two years, Dr. Unger’s research has shifted to type 1 diabetes. He has reported on a novel method for extending the survival of islet transplanted into the livers of type 1 diabetic recipients. These studies led to the discovery that leptin, which prevented the loss of function of islet transplants, also normalized the blood glucose levels in type 1 diabetic animals that had never received islets. Thus, leptin normalizes glucose in type 1 diabetes–the first such substance to do so since the discovery of insulin in 1922. After completing the animal experiments, Dr. Unger plans to apply for permission to begin human studies, in the hope that leptin treatment can replace insulin therapy and improve the quality of life for type 1 patients.
A. Vidal-Puig University of Cambridge Metabolic Research Laboratories, Cambridge, UK E-mail address: [email protected]. Corresponding author. Roger H. Unger The University of Texas Southwestern Medical Center, Dallas, USA E-mail address: [email protected]. Corresponding author. Corresponding author.The University of Texas Southwestern Medical Center, Dallas, USA