Biochimie 96 (2014) 1e2
Contents lists available at ScienceDirect
Biochimie journal homepage: www.elsevier.com/locate/biochi
Editorial
Lipids in metabolic diseases Metabolic diseases are the consequences of dysregulated metabolic pathways due to alterations in nutritional input, energy storage, release or dissipation, hormone response, cell signaling and/or the occurrence of genetic mutations. Lipids and lipid derivatives play important roles in all these processes. For instance, fatty acid (FA) species in nutritional oils act as taste molecules to signal their occurrence to the brain. The various FAs also exert alternate effects in cells, starting with enterocytes in which they affect the production of chylomicrons. The role of lipids as structural species can be emphasized, particularly in membrane domains. FA storage in adipose tissue and their release on demand as well as their mitochondrial beta-oxidation are clearly key targets for energetic alterations. The quality of FAs determines their bioavailability, their capacity to produce various bioactive lipids and their differential involvement as signaling intermediates. Last but not least, genetic mutations can impact enzyme reactions. In the current Biochimie special issue, expert researchers gather together their knowledge to give an overview of these various aspects and to describe the more recent aspects of the influence of lipids in metabolic diseases. The oro-sensory perception of fat is an important process with Public Health issues. Fat taste is submitted to regulatory processes that are stylishly described in the first two review articles, one from Besnard’s team who gives an overview of the field and the other from Khan’s group who analyzes the role of calcium signaling in taste bud cells. The various FA species present in the diet not only affect the taste and its signaling to the brain, it has also physiological and pathological consequences. This topic is reviewed by the groups of Philippe Legrand and of Jerôme Bellenger with the emphasis put respectively on the role of dietary linoleic acid on inflammation and on the evaluation of n-3 PUFAs as protectors against breast cancer, using the fat-1 transgenic mouse model. Nutrient intake of FA species varies depending on the composition of vegetable oils. An original paper from the Chapman laboratory tackles this problem with the modification of oleic acid content in cottonseed embryos using a genetic approach. FAs are lipophilic compounds that bind different types of carriers and receptors/transporters. Isabelle Niot and her colleagues report the existence in the intestine of various lipid binding proteins (LBP) and discuss the physiological contribution of each of these proteins in the absorption of long-chain FAs together with their reassembly into chylomicrons, the triglyceride-rich lipoproteins that contribute primarily to the serum lipid level. In addition, the role of lipid droplets in chylomicron synthesis and in other previously unsuspected functions is stressed by Sylvie Demignot and her collaborators in an elegant review article. In contrast, highdensity lipoproteins are triglyceride-poor particles that exert cardioprotective effects highlighted by Maïga et al. in this issue. Michel 0300-9084/$ e see front matter Ó 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.biochi.2013.11.009
Record and his colleagues timely focus their manuscript on another type of lipidic structure released by cells in addition to lipoproteins, namely the exosomes. These nanovesicles transfer intracellular materials, including lipids, from cell to cell. Their involvement in cholesterol-related diseases is highlighted herein. Micro- and nano-membrane domains that are rich in cholesterol and sphingolipids play pivotal roles in cell physiology. Defects in the biosynthesis and recycling of such membrane domains can alter brain function and global lipid homeostasis as described in a review from Thierry Galli and Diana Molino. Lipids are transported between membranes in intracellular compartments. The proteins that favor lipid exchanges are named StAR related proteins (START). This large family of proteins is fascinating and it was shown that mutations or deregulated expression of STARTs was linked to pathologies like autoimmune diseases and cancers. These aspects and the START-related transfer mechanisms are extensively reviewed in a paper from Fabien Alpy and Catherine Tomasetto. We decided to advertise these proteins in the front cover of the current issue. In a cornerstone article entitled “what if Minkowski had been ageusic ? an alternative angle on diabetes”, published in 1992 in the journal Science (vol 258, pp 766e770), the late Denis McGarry suggested that our historical perception of the metabolic derangement in diabetes had carried the wrong emphasis. If Minkowski had lacked the sense of taste but had a good nose, he would have smelled the acetone from ketone bodies in the urine instead of detecting sugar. He would then concluded that insulin resistance and ultimately diabetes were secondary to disordered lipid metabolism. In line with this concept, a series of papers are focused on the regulation of FA metabolism, starting with the role of lipid droplet (LD) coat proteins, the perilipins. The functions exerted by perilipins are stylishly explained in a manuscript from Carole Sztalryd and Alan Kimmel that reviews the current knowledge of this family of proteins in regulating tissue-specific LDs and their link to energy storage and expenditure. Along the same line of thought, one of us (Isabelle Dugail) puts emphasis on the very recent and important discovery of the interplay between LDs and lysosomes e in a process named lipophagy e and the potential role of this activity in metabolic diseases and inflammation. White adipose tissue is the site of FA storage and release. It provides FAs to the blood during fasting. The impact of the most recently described triglyceride hydrolase e the adipocyte triglyceride lipase or ATGL e is described in a noteworthy manuscript from Kratky’s group, analyzing the consequences of ATGL deficiency on mitochondrial dysfunction. The regulation of mitochondrial beta-oxidation plays indeed a key role in FA catabolism and any defect in that process may result in severe clinical manifestations, particularly when muscles are concerned. These
2
Editorial / Biochimie 96 (2014) 1e2
aspects are covered in the paper by one of the leaders in this competitive field of research, Jean Bastin, who was first to demonstrate with his collaborators that certain fibrates can restore either LCFA import into mitochondria or beta-oxidation in cells from humans with inborn deficiencies in these pathways. Such a discovery opens up new avenues in pharmacological therapies. Besides adipose tissue and muscles, the liver is one of the insulinsensitive tissues with important metabolic functions. In an excellent review paper, Groen’s laboratory sheds light on the role of the zonation of lipid and glucose metabolism in the liver on insulin resistance and hepatosteatosis. The influence of cytokines on lipid metabolism is now well established, starting with adipocytederived cytokine. The leader in this area of investigations, Philipp Scherer, made the original discovery of adiponectin and deciphered the role of this adipokine in lipid metabolism and associated diseases. In the current issue, Philipp Scherer and coauthors put to the fore the critical influence of adipokines on the steady-state level of sphingolipids, with a special highlight on ceramide catabolism in insulin resistance, an emerging field in metabolism research. Cell signaling through phospholipases can deeply influence metabolism. Autotaxin is a secreted lysophospholipase D that allows lysophosphatidic acid synthesis. The connection between autotaxin and impaired glucose homeostasis is thoroughly reviewed in a manuscript from the laboratory of Jean-Sébastien Saulnier-Blache, an expert in this field. Phosphoinositide-specific phospholipase C (PIePLC) plays also a key role in lipid signaling. Plant PIePLCs are the subject of extensive studies. Eric Ruelland and his collaborators demonstrate in their manuscript that learning how plant PIePLCs function can have an impact on the general signaling pathways transduced by these proteins in animals. Phospholipases are regulated by very interesting neuropeptides, the orexins, the subject of a contribution by Jyrki Kukkonen. This special issue ends with an exciting review article on seipin by Xavier Prieur and colleagues. Mutations in seipin was identified in 2001 by Jocelyne Magré and collaborators as the cause of Berardinelli-Seip congenital lipodystrophy, which is characterized by almost no adipose tissue and severe insulin-resistance. The present paper analyses the mechanism of seipin action and discusses the validity of mice models to test pharmaceutical approaches that could be applied to humans.
All the above-mentioned articles of this Biochimie special issue were the subject of presentations at the 9th Lipidomics Meeting “Lipids & Metabolic Diseases” that was organized by the “Groupe d’Etude et de Recherche en Lipidomique (GERLI)” in Paris in October 2012. We thank all authors for their contributions. Isabelle Dugail Institut National de la Santé et de la Recherche Médicale UMR-S 872, Centre de recherche des Cordeliers, Eq 7, 15 rue de l’école de médecine, 75006 Paris, France E-mail address: [email protected]. Athina Kalopissis Institut National de la Santé et de la Recherche Médicale U872, Centre de Recherche des Cordeliers, Eq 4, 15 rue de l’école de médecine, 75006 Paris, France E-mail address: [email protected]. Martine Miquel Institut Jean-Pierre Bourgin, UMR 1318 INRA-AgroParis Tech, ERL CNRS n 3559, INRA Centre de Versailles-Grignon, Route de Saint Cyr, 78026 Versailles Cedex, France E-mail address: [email protected]. Dominique Rainteau ERL Institut National de la Santé et de la Recherche Médicale U 1057/UMR 7203, Université Pierre et Marie Curie, Faculté de Médecine CHU Saint-Antoine, 27, rue Chaligny, 75571 Paris Cedex 12, France E-mail address: [email protected]. Alain Zachowski Laboratoire de Physiologie Cellulaire et Moléculaire des Plantes, UR 5-EAC 7180 CNRS, Université Pierre et Marie Curie, 4 place Jussieu, 75252 Paris Cedex 05, France E-mail address: [email protected]. Claude Forest* Institut National de la Santé et de la Recherche Médicale UMR-S 747, Université Paris Descartes, Pharmacologie Toxicologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France * Corresponding
author. Tel.: +33 1 42863867; fax: +33 1 42863868. E-mail address: [email protected] (C. Forest).
Contents lists available at ScienceDirect
Biochimie journal homepage: www.elsevier.com/locate/biochi
Editorial
Lipids in metabolic diseases Metabolic diseases are the consequences of dysregulated metabolic pathways due to alterations in nutritional input, energy storage, release or dissipation, hormone response, cell signaling and/or the occurrence of genetic mutations. Lipids and lipid derivatives play important roles in all these processes. For instance, fatty acid (FA) species in nutritional oils act as taste molecules to signal their occurrence to the brain. The various FAs also exert alternate effects in cells, starting with enterocytes in which they affect the production of chylomicrons. The role of lipids as structural species can be emphasized, particularly in membrane domains. FA storage in adipose tissue and their release on demand as well as their mitochondrial beta-oxidation are clearly key targets for energetic alterations. The quality of FAs determines their bioavailability, their capacity to produce various bioactive lipids and their differential involvement as signaling intermediates. Last but not least, genetic mutations can impact enzyme reactions. In the current Biochimie special issue, expert researchers gather together their knowledge to give an overview of these various aspects and to describe the more recent aspects of the influence of lipids in metabolic diseases. The oro-sensory perception of fat is an important process with Public Health issues. Fat taste is submitted to regulatory processes that are stylishly described in the first two review articles, one from Besnard’s team who gives an overview of the field and the other from Khan’s group who analyzes the role of calcium signaling in taste bud cells. The various FA species present in the diet not only affect the taste and its signaling to the brain, it has also physiological and pathological consequences. This topic is reviewed by the groups of Philippe Legrand and of Jerôme Bellenger with the emphasis put respectively on the role of dietary linoleic acid on inflammation and on the evaluation of n-3 PUFAs as protectors against breast cancer, using the fat-1 transgenic mouse model. Nutrient intake of FA species varies depending on the composition of vegetable oils. An original paper from the Chapman laboratory tackles this problem with the modification of oleic acid content in cottonseed embryos using a genetic approach. FAs are lipophilic compounds that bind different types of carriers and receptors/transporters. Isabelle Niot and her colleagues report the existence in the intestine of various lipid binding proteins (LBP) and discuss the physiological contribution of each of these proteins in the absorption of long-chain FAs together with their reassembly into chylomicrons, the triglyceride-rich lipoproteins that contribute primarily to the serum lipid level. In addition, the role of lipid droplets in chylomicron synthesis and in other previously unsuspected functions is stressed by Sylvie Demignot and her collaborators in an elegant review article. In contrast, highdensity lipoproteins are triglyceride-poor particles that exert cardioprotective effects highlighted by Maïga et al. in this issue. Michel 0300-9084/$ e see front matter Ó 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.biochi.2013.11.009
Record and his colleagues timely focus their manuscript on another type of lipidic structure released by cells in addition to lipoproteins, namely the exosomes. These nanovesicles transfer intracellular materials, including lipids, from cell to cell. Their involvement in cholesterol-related diseases is highlighted herein. Micro- and nano-membrane domains that are rich in cholesterol and sphingolipids play pivotal roles in cell physiology. Defects in the biosynthesis and recycling of such membrane domains can alter brain function and global lipid homeostasis as described in a review from Thierry Galli and Diana Molino. Lipids are transported between membranes in intracellular compartments. The proteins that favor lipid exchanges are named StAR related proteins (START). This large family of proteins is fascinating and it was shown that mutations or deregulated expression of STARTs was linked to pathologies like autoimmune diseases and cancers. These aspects and the START-related transfer mechanisms are extensively reviewed in a paper from Fabien Alpy and Catherine Tomasetto. We decided to advertise these proteins in the front cover of the current issue. In a cornerstone article entitled “what if Minkowski had been ageusic ? an alternative angle on diabetes”, published in 1992 in the journal Science (vol 258, pp 766e770), the late Denis McGarry suggested that our historical perception of the metabolic derangement in diabetes had carried the wrong emphasis. If Minkowski had lacked the sense of taste but had a good nose, he would have smelled the acetone from ketone bodies in the urine instead of detecting sugar. He would then concluded that insulin resistance and ultimately diabetes were secondary to disordered lipid metabolism. In line with this concept, a series of papers are focused on the regulation of FA metabolism, starting with the role of lipid droplet (LD) coat proteins, the perilipins. The functions exerted by perilipins are stylishly explained in a manuscript from Carole Sztalryd and Alan Kimmel that reviews the current knowledge of this family of proteins in regulating tissue-specific LDs and their link to energy storage and expenditure. Along the same line of thought, one of us (Isabelle Dugail) puts emphasis on the very recent and important discovery of the interplay between LDs and lysosomes e in a process named lipophagy e and the potential role of this activity in metabolic diseases and inflammation. White adipose tissue is the site of FA storage and release. It provides FAs to the blood during fasting. The impact of the most recently described triglyceride hydrolase e the adipocyte triglyceride lipase or ATGL e is described in a noteworthy manuscript from Kratky’s group, analyzing the consequences of ATGL deficiency on mitochondrial dysfunction. The regulation of mitochondrial beta-oxidation plays indeed a key role in FA catabolism and any defect in that process may result in severe clinical manifestations, particularly when muscles are concerned. These
2
Editorial / Biochimie 96 (2014) 1e2
aspects are covered in the paper by one of the leaders in this competitive field of research, Jean Bastin, who was first to demonstrate with his collaborators that certain fibrates can restore either LCFA import into mitochondria or beta-oxidation in cells from humans with inborn deficiencies in these pathways. Such a discovery opens up new avenues in pharmacological therapies. Besides adipose tissue and muscles, the liver is one of the insulinsensitive tissues with important metabolic functions. In an excellent review paper, Groen’s laboratory sheds light on the role of the zonation of lipid and glucose metabolism in the liver on insulin resistance and hepatosteatosis. The influence of cytokines on lipid metabolism is now well established, starting with adipocytederived cytokine. The leader in this area of investigations, Philipp Scherer, made the original discovery of adiponectin and deciphered the role of this adipokine in lipid metabolism and associated diseases. In the current issue, Philipp Scherer and coauthors put to the fore the critical influence of adipokines on the steady-state level of sphingolipids, with a special highlight on ceramide catabolism in insulin resistance, an emerging field in metabolism research. Cell signaling through phospholipases can deeply influence metabolism. Autotaxin is a secreted lysophospholipase D that allows lysophosphatidic acid synthesis. The connection between autotaxin and impaired glucose homeostasis is thoroughly reviewed in a manuscript from the laboratory of Jean-Sébastien Saulnier-Blache, an expert in this field. Phosphoinositide-specific phospholipase C (PIePLC) plays also a key role in lipid signaling. Plant PIePLCs are the subject of extensive studies. Eric Ruelland and his collaborators demonstrate in their manuscript that learning how plant PIePLCs function can have an impact on the general signaling pathways transduced by these proteins in animals. Phospholipases are regulated by very interesting neuropeptides, the orexins, the subject of a contribution by Jyrki Kukkonen. This special issue ends with an exciting review article on seipin by Xavier Prieur and colleagues. Mutations in seipin was identified in 2001 by Jocelyne Magré and collaborators as the cause of Berardinelli-Seip congenital lipodystrophy, which is characterized by almost no adipose tissue and severe insulin-resistance. The present paper analyses the mechanism of seipin action and discusses the validity of mice models to test pharmaceutical approaches that could be applied to humans.
All the above-mentioned articles of this Biochimie special issue were the subject of presentations at the 9th Lipidomics Meeting “Lipids & Metabolic Diseases” that was organized by the “Groupe d’Etude et de Recherche en Lipidomique (GERLI)” in Paris in October 2012. We thank all authors for their contributions. Isabelle Dugail Institut National de la Santé et de la Recherche Médicale UMR-S 872, Centre de recherche des Cordeliers, Eq 7, 15 rue de l’école de médecine, 75006 Paris, France E-mail address: [email protected]. Athina Kalopissis Institut National de la Santé et de la Recherche Médicale U872, Centre de Recherche des Cordeliers, Eq 4, 15 rue de l’école de médecine, 75006 Paris, France E-mail address: [email protected]. Martine Miquel Institut Jean-Pierre Bourgin, UMR 1318 INRA-AgroParis Tech, ERL CNRS n 3559, INRA Centre de Versailles-Grignon, Route de Saint Cyr, 78026 Versailles Cedex, France E-mail address: [email protected]. Dominique Rainteau ERL Institut National de la Santé et de la Recherche Médicale U 1057/UMR 7203, Université Pierre et Marie Curie, Faculté de Médecine CHU Saint-Antoine, 27, rue Chaligny, 75571 Paris Cedex 12, France E-mail address: [email protected]. Alain Zachowski Laboratoire de Physiologie Cellulaire et Moléculaire des Plantes, UR 5-EAC 7180 CNRS, Université Pierre et Marie Curie, 4 place Jussieu, 75252 Paris Cedex 05, France E-mail address: [email protected]. Claude Forest* Institut National de la Santé et de la Recherche Médicale UMR-S 747, Université Paris Descartes, Pharmacologie Toxicologie et Signalisation Cellulaire, 45 rue des Saints Pères, 75006 Paris, France * Corresponding
author. Tel.: +33 1 42863867; fax: +33 1 42863868. E-mail address: [email protected] (C. Forest).
