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Lipidomics: Making sense of the data lode
Chemistry and Physics of Lipids 164S (2011) S1–S4
Contents lists available at ScienceDirect
Chemistry and Physics of Lipids journal homepage: www.elsevier.com/locate/chemphyslip
Plenary Lectures (PL 1–25) and Short Oral Communications (SO 1–24)
Session 1: Lipids in molecular medicine PL 2
15th Laurens van Deenen Lecture PL 1
A role for skin stearoyl-CoA desaturase-1 in obesity and diabetes James Ntambi
Lipidomics: Making sense of the data lode
Department of Biochemistry, University of Wisconsin, Madison, USA
Peter Quinn
Obesity and diabetes develop as a complex result of genetic, metabolic and environmental factors and are characterized by increased lipogenesis and lipid accumulation in many tissues. A critical regulator of lipogenesis is stearoyl-CoA desaturase (SCD), which catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleoyl- (18:1n9) and palmitoleoyl-CoA (16:1n7). These MUFAs are the major fatty acid substrates for the synthesis of triglycerides, cholesterol esters, phospholipids and wax esters. SCD expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess 18:1n9 or 16:1n7 synthesis may contribute to metabolic disease development. Mice with a global deletion of SCD1 isoform (GKO) are resistant to diet- and genetically-induced obesity, insulin resistance and liver steatosis. This phenotype is complex due to SCD1 deficiency and the associated metabolic changes occurring in many organs simultaneously. Our long-term goal is to determine the tissue-specific contribution of SCD1 to the metabolic and genetic changes associated with obesity and the metabolic syndrome. We have found that deletion of skin SCD1 (SKO mice) recapitulated the skin abnormalities observed in GKO mice and protected SKO mice from high-fat diet-induced obesity, hepatic triglyceride accumulation and glucose intolerance regardless of changes in ambient temperature suggesting that the hypermetabolic phenotype is not simply due to accelerated heat loss to the environment. However, SKO mice maintain normal expression of SCD1 in liver and adipose, indicating that SCD1 deletion from liver and/or adipose is not required for obesity resistance. Microarray analysis of skin gene expression in mice fed a standard rodent diet revealed a robust elevation of skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. Furthermore, human SEB-1 sebocytes treated with retinol and an SCD inhibitor also display an elevation in retinoic acidinduced genes. These findings indicate that absence of skin SCD1 in the sebaceous glands is sufficient to enhance whole-body energy expenditure and elicit protection from high-fat diet-induced obesity and insulin resistance. This also highlights a novel role for skin lipid synthesis in the regulation of energy expenditure, food intake and the development of obesity.
Department of Biochemistry, King’s College London, London, UK Laurens van Deenen was a giant in the lipid field upon whose shoulders we stand today. He remarked some fifty years ago that significant steps had been made in the characterisation of membrane lipids by the introduction of ‘modern’ chromatography and electrophoretic methods. His lament at the time was that knowledge of their physical properties had not kept pace with these developments. He then set about on a distinguished career to synthesize pure molecular species of polar lipids and report on their properties. The advances in technology that has taken place in the interim would have been unimaginable at the outset of his endeavours. The advent of mass spectrometry generating a plethora of data from miniscule amounts of tissue has revolutionized the field of lipid analysis. As then, however, we are still struggling to keep pace with the biophysical characterisation of the different molecular species of lipid that turn up in tissue analyses. This knowledge is essential if we are to address fundamental questions like why are there so many different lipids in cell membranes? How are the biochemical mechanisms responsible for homeostatic regulation of the amounts of each membrane lipid, in turn, controlled? What are the molecular mechanisms underlying the role of lipids in transmembrane signal transduction? The answers to some of these questions have been forthcoming from synchrotron X-ray and neutron scattering methods. An overview of developments in the biophysical properties of lipids extracted from biological tissues will be presented. doi:10.1016/j.chemphyslip.2011.05.031
doi:10.1016/j.chemphyslip.2011.05.032 0009-3084/$ – see front matter
Contents lists available at ScienceDirect
Chemistry and Physics of Lipids journal homepage: www.elsevier.com/locate/chemphyslip
Plenary Lectures (PL 1–25) and Short Oral Communications (SO 1–24)
Session 1: Lipids in molecular medicine PL 2
15th Laurens van Deenen Lecture PL 1
A role for skin stearoyl-CoA desaturase-1 in obesity and diabetes James Ntambi
Lipidomics: Making sense of the data lode
Department of Biochemistry, University of Wisconsin, Madison, USA
Peter Quinn
Obesity and diabetes develop as a complex result of genetic, metabolic and environmental factors and are characterized by increased lipogenesis and lipid accumulation in many tissues. A critical regulator of lipogenesis is stearoyl-CoA desaturase (SCD), which catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleoyl- (18:1n9) and palmitoleoyl-CoA (16:1n7). These MUFAs are the major fatty acid substrates for the synthesis of triglycerides, cholesterol esters, phospholipids and wax esters. SCD expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess 18:1n9 or 16:1n7 synthesis may contribute to metabolic disease development. Mice with a global deletion of SCD1 isoform (GKO) are resistant to diet- and genetically-induced obesity, insulin resistance and liver steatosis. This phenotype is complex due to SCD1 deficiency and the associated metabolic changes occurring in many organs simultaneously. Our long-term goal is to determine the tissue-specific contribution of SCD1 to the metabolic and genetic changes associated with obesity and the metabolic syndrome. We have found that deletion of skin SCD1 (SKO mice) recapitulated the skin abnormalities observed in GKO mice and protected SKO mice from high-fat diet-induced obesity, hepatic triglyceride accumulation and glucose intolerance regardless of changes in ambient temperature suggesting that the hypermetabolic phenotype is not simply due to accelerated heat loss to the environment. However, SKO mice maintain normal expression of SCD1 in liver and adipose, indicating that SCD1 deletion from liver and/or adipose is not required for obesity resistance. Microarray analysis of skin gene expression in mice fed a standard rodent diet revealed a robust elevation of skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. Furthermore, human SEB-1 sebocytes treated with retinol and an SCD inhibitor also display an elevation in retinoic acidinduced genes. These findings indicate that absence of skin SCD1 in the sebaceous glands is sufficient to enhance whole-body energy expenditure and elicit protection from high-fat diet-induced obesity and insulin resistance. This also highlights a novel role for skin lipid synthesis in the regulation of energy expenditure, food intake and the development of obesity.
Department of Biochemistry, King’s College London, London, UK Laurens van Deenen was a giant in the lipid field upon whose shoulders we stand today. He remarked some fifty years ago that significant steps had been made in the characterisation of membrane lipids by the introduction of ‘modern’ chromatography and electrophoretic methods. His lament at the time was that knowledge of their physical properties had not kept pace with these developments. He then set about on a distinguished career to synthesize pure molecular species of polar lipids and report on their properties. The advances in technology that has taken place in the interim would have been unimaginable at the outset of his endeavours. The advent of mass spectrometry generating a plethora of data from miniscule amounts of tissue has revolutionized the field of lipid analysis. As then, however, we are still struggling to keep pace with the biophysical characterisation of the different molecular species of lipid that turn up in tissue analyses. This knowledge is essential if we are to address fundamental questions like why are there so many different lipids in cell membranes? How are the biochemical mechanisms responsible for homeostatic regulation of the amounts of each membrane lipid, in turn, controlled? What are the molecular mechanisms underlying the role of lipids in transmembrane signal transduction? The answers to some of these questions have been forthcoming from synchrotron X-ray and neutron scattering methods. An overview of developments in the biophysical properties of lipids extracted from biological tissues will be presented. doi:10.1016/j.chemphyslip.2011.05.031
doi:10.1016/j.chemphyslip.2011.05.032 0009-3084/$ – see front matter