Obesity risk quantification: Lipidomic BMI better than traditional BMI

Obesity is a prime threat to human health. In daily healthcare practice, the go-to indicator of overweight and obesity is the body mass index (BMI). Now, an international team of scientists led by Lipotype introduces a revolutionary A.I. BMI approach towards personalized and precision medicine.


A joint effort of academy and industry
When academy meets industry significant jumps towards the future are possible. Researchers from TU Dresden and Lipotype GmbH, a spin-off of the Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, with the international participation of scientists from Lund University (Sweden) and National Institute for Health and Welfare (Finland) teamed up to critically investigate the BMI of more than 1000 patients. The international research team applied advanced artificial intelligence tools to develop an algorithm which makes use of the human blood plasma lipid composition, the plasma lipidome.


The lipidomic BMI
The plasma lipidome contains hundreds of distinct lipids. “Together, they are valuable indicators to explore the state of metabolism health of an individual – like a health fingerprint”, explains Mathias Gerl from Lipotype. This lipidomic data was used for training the algorithm to predict the BMI of each patient.

In comparison to the ‘household measures’-based BMI, the lipidomic data provided the new algorithm with the power to propose a new ‘molecular lipidomic BMI’. The lipidomic BMI calculation revealed that the molecular BMI was in a number of cases significantly higher than the traditional BMI. In approximately 1 out of 7 patients, the lipidomic BMI improved the classic ‘morphometric BMI’, and provided more information about obesity compared to the traditional BMI measurement, e.g. about the amount of visceral fat, a harmful kind of fat deposit.


The future of BMI
“Long-time consequences can occur when a patient in need for a weight reducing therapy to combat the risk for obesity-associated disease is sent home without remedy”, states Olle Melander from Lund University. “These patients may suddenly suffer from a heart attack at age 40 leaving their doctors puzzled”, comments Carlo Vittorio Cannistraci from the Biotechnology Center (BIOTEC) at the TU Dresden and adds: “We should overcome the obsolete logic that a single marker can help to assess risk in complex systems such as humans. Computational biomedicine adopts artificial intelligence to design multidimensional markers composed of many variables that increase precision of diagnosis. Hence, we hope that the traditional BMI will be replaced with a lipidomic marker to outpace the misclassification of 14% of patients.”


Resources

1 – Publication: Machine learning of human plasma lipidomes for obesity estimation in a large population cohort
2 – Press Release: Obesity risk quantification, a jump towards the future
3 – Pressemitteilung: Adipositas-Risikobestimmung, ein Sprung in die Zukunft
4 – TV news: Blutanalyse soll bei Erkennung von Adipositas helfen (only available until October 28)


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Prof. Anne-Claude Gavin accepts 1st prize of LEA

The laureate of the world’s first Lipidomics Excellence Award, Prof. Dr. Anne-Claude Gavin from the University of Geneva , uses the analysis technology of Dresden based Lipotype GmbH for the next breakthrough in her lipid transfer research. The biochemist draws the world’s first molecular “map of lipid highways”, she is tracing the ways of lipid transfer between the membranes of body cells.


A map of lipid highways
“Latest research shows that the lipid metabolism plays a major role in the development of diabetes, cancer or Alzheimer’s. Once we have a better understanding of the ways certain lipids cause which effect, we may pave the way for new potential treatment approaches”, the laureate explains her research goal. “Lipidomics helps us answering questions we would not even dare to ask without it. It opens doors that may hold the answer to our civilization diseases.”


Lipidomics in diabetes research
Life science researchers of various disciplines discover Lipotype’s Shotgun Lipidomics Analysis for their projects. So does the diabetes research: “Lipidomics is step by step revealing processes and connections that stay hidden with traditional analysis methods”, says Prof. Dr. Michele Solimena, Professor of Molecular Diabetology, Medical School, TU Dresden, Germany and Director of the Paul Langerhans Institute Dresden, a German Center for Diabetes Research. „In diabetes research we make good progress thanks to lipidomics, e.g. it is now possible to define molecular lipid signatures that tell us about the development of non-diabetic to diabetes type 2 and progression towards diabetes complications.”


Deeper insights into the lipid cosmos
The unique Lipidomics Excellence Award rewards innovation and the drive for novelty in researchers who strike out in a new direction using lipidomics. The winner Prof. Dr. Anne-Claude Gavin’s project idea stood out in a strong competition with numerous international scientists and research teams. Ultimately, a top-class independent jury of renowned lipidomics experts awarded the Geneva-based scientist with the first prize equalizing lipid analyses worth 50,000 EUR.

“We want to shine a light on the fact that lipid analyses really make the difference between research and groundbreaking research: by providing new data one gains an even deeper insight into the lipid cosmos. It is high time to seize the potentials. Let us see what there is still to discover“, says Prof. Dr. Kai Simons, Professor and Director Emeritus at Max-Planck-Institute for Molecular Cell Biology and Genetics Dresden and founder and CEO of Lipotype.


About LEA
LEA, the Lipidomics Excellence Award, promotes researchers who are eager to contribute to the progress of life sciences with generous research prizes. Three individuals with ongoing research are awarded to support their projects. Applications were open to all researchers from academia and industry.

The winner of the first prize received 55,000 EUR worth of analysis services and present their research at the EMBO Workshop “Lipid function in health and disease” (27.-30.09.2019). A press conference was hold to
present the project and formally handover the LEA 2019 trophy.

LEA is supported by LIPID MAPS, SwissLipids and Lipotype, and the media Journal of Lipid Research, LABO and transkript.


Resources

1 – Materials: Additional press material including photos
2 – Website: The winners of LEA 2019
3 – Press Release: Summary of the Lipidomics Excellence Award press talk
4 – Pressemitteilung: Zusammenfassung der “Lipidomics Excellence Award”-Pressekonferenz


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The month of August in Lipidomics Publications

The month of August came with a set of newly-published lipidomics publications which made use of Lipotype Shotgun Lipidomics.


Chronic kidney disease
Clinical risk factors explain only a fraction of the variability of eGFR decline in people with type 2 diabetes. However, cross-omics technologies have the potential to identify additional biomarkers for the refinement of prognosis.

Putting together proteomics, metabolomics and lipidomics panel assay measurements and the clinical factor eGFR, the investigation unraveled the predictor biomarker KIM-1.

This is the first publication of the BEAt-DKD consortium which receives funding under IMI of the EU.


Nano-scale lipid organization
The plasma membrane is composed of a complex lipid mixture that forms heterogeneous membrane environments. Physiological events are controlled by small-scale lipid organization.

The investigation unraveled that some proteins are critical for the synthesis of the lipid phosphatidylinositol (4,5)-bisphosphate, a key regulator of dynamic events at the plasma membrane. Ultimately, they control global plasma membrane organization and dynamics.


Lipid droplet size
Lipid droplet breakdown in hepatocytes (liver cells) is mediated by a combination of lipolysis and a selective autophagic mechanism called lipophagy. However, the relationship of these seemingly distinct pathways remained unclear – until now.

This study found that inhibition of lipolysis, lipophagy, or both resulted in similar overall lipid droplet content but dramatic differences in their form. Inhibition of the lipolysis enzyme ATGL resulted in large cytoplasmic lipid droplets, whereas lysosomal inhibition caused the accumulation of numerous small ones within the cytoplasm. The combination of both resulted in large droplets.


Alterations of the liver in diabetes
The liver regulates the availability of insulin to other tissues. It is the first organ physiologically exposed to higher insulin concentrations. The molecular consequences of chronic insulin deficiency for the liver have now been studied systematically.

The analyses revealed increased activities in amino acid metabolism, oxidation of fatty acids, ketogenesis, and gluconeogenesis in the liver samples. The first multi-omics study of a clinically relevant diabetic large animal model revealed molecular signatures and key drivers of functional alterations of the liver in insulin-deficient diabetes.


Resources

1 – Integrative analysis of prognostic biomarkers derived from multiomics panels helps discrimination of chronic kidney disease trajectories in people with type 2 diabetes
2 – Osh Proteins Control Nanoscale Lipid Organization Necessary for PI(4,5)P2 Synthesis
3 – Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes
4 – Multi-omics insights into functional alterations of the liver in insulin-deficient diabetes mellitus


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First large-scale study of the genetics of human plasma lipid species

Understanding the genetics of lipid species offers information beyond that provided by routine lipid screening, and can help improve risk prediction and treatment. In the first large-scale study, novel lipid-associated genetic variants were identified, some of which were linked with risk for cardiovascular disease, such as heart attacks and strokes. Lipotype provided the technology to measure these lipids – Lipotype Shotgun Lipidomics.


The human blood plasma lipidome
Human plasma comprises hundreds of lipid species which differ in chemical structure and function. Many of these are known risk factors for human diseases. Advances in mass spectrometry-driven lipid analysis – lipidomics – has made it possible to study the patient lipidome to a greater extent than is possible with conventional analytical methods. Currently, however, understanding the genetic regulation of molecular lipid species is lacking. Unraveling this information could help in the personalized management of atherosclerosis and heart disease.

In light of this, this collaborative project involving centres in Finland, Germany and the USA integrated information from the lipidome, genome and phenome to answer key questions relating to the heritability of lipid species, including: Which genetic variants influence plasma levels of lipid species? How do these variants relate to disease outcomes and what is the underlying mechanisms?


The answers are…
1. Lipid species are heritable.
Lipid species heritability ranges from 10 to 54 per cent, with the highest heritability in lipids containing polyunsaturated fatty acids (PUFAs). These findings are important given renewed interest in the role of PUFAs in cardiovascular disease.

2. GWAS analyses identified 35 gene variants associated with lipids.
Using clinical outcome data, the investigators showed that 10 of these variants were associated with cardiovascular disease. In addition, 3 gene variants at the were associated with type 2 diabetes. This information could help drive the development of new treatment targets.

3. Further notes on lipid metabolism.
The study also provided clues to the underlying mechanisms of well-known lipid loci on lipid metabolism and cardiovascular disease risk.


Resources

Press Release: First large-scale study of the genetics of human plasma lipid species
Publication: Genetics of human plasma lipidome to understand lipid metabolism and its link to diseases beyond traditional lipids


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LEA Jury announces Winners of LEA 2019

LEA, the Lipidomics Excellence Award, was founded to strengthen life sciences through lipidomics. Over the course of April, the LEA jury deliberated on the submitted projects to announce the three LEA awardees.


LEA 2019 research prizes
LEA, promotes researchers who are eager to contribute to the progress of life sciences with generous research prizes. The winner of the first prize receives a trophy, 50,000 EUR worth of analysis services and a speaking slot to present their results at the EMBO workshop “Lipid function in health and disease” as well as coverage of the logistical costs to participate in the workshop. The second prize winner is awarded a lipidomics analysis worth 10,000 EUR; the third prize winner is acknowledged by a 1,500 EUR analysis package. (All lipidomics analysis packages are provided by Lipotype GmbH.)

The independent LEA jury composed of Britta Brügger, Pietro De Camilli, Ari Helenius and Kai Simons discussed vividly the LEA 2019 applications. After a month of deliberation, they decided on the following three scientists and their research projects.


The winners are…
1. Prize of LEA 2019 goes to…
Prof. Anne-Claude Gavin and her lipid-transfer research project. She will investigate lipid movements to develop the first molecular cartography of lipid “highways”.

2. Prize of LEA 2019 is awarded to…
Dr. Oliver Schmidt and his newly discovered EGAD protein degradation pathway. He will research how EGAD influences lipid metabolism to improve our understanding of cellular homeostasis.

3. Prize of LEA was won by…
Prof. Sarah L. Keller for her research in membranes of yeast. She will investigate how lipids drive domain formation in cell membranes.

All research project details are outlined here.


Resources

Press Release: LEA Jury announces Winners of LEA 2019
Press Release: LEA Jury gibt Sieger des LEA 2019 bekannt


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Lipotype is GMP certified!

Good Manufacturing Practices (GMP) ensure safety and quality of pharmaceutical products. Lipotype is the worldwide first and only officially GMP certified shotgun lipidomics service provider for pharmaceutical applications.


The need for GMP regulations
Quality variations can pose direct threats to patient health – especially in the pharma industry. This is why quality control plays a central role in manufacturing and developing pharmaceutical products. GMP certifications are issued by governmental authorities to ensure product quality and compliance with mandatory health agency requirements.

As worldwide first and only shotgun lipidomics service provider with official GMP certificate by state authority, Lipotype now offers untargeted, global and absolutely quantitative lipidomics analysis services according to GMP regulation laid down in Directive 2003/94/EC.


GMP-compliant lipidomics services
Pharma researchers challenging therapeutic limitations by developing new pharmaceutical products can draw on Lipotype Shotgun Lipidomics services beyond lipidomic analysis of content, purity and stability. Development of GMP compliant analytical tests and release analysis of compounds from clinical trials to market release complete the portfolio of GMP certified lipid analysis services.


Resources

Press Release: Worldwide first and only shotgun lipidomics service provider with official GMP certificate


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New method for molecular profiling of adipose tissue

The Paul Langerhans Institute Dresden, a partner of the DZD, and the University Hospital Carl Gustav Carus joined their forces with Lipotype GmbH and developed a new shotgun lipidomics method for the molecular profiling of brown and white adipose tissue. The results of this collaborative work have now been published in the journal ́Molecular Metabolism ́.


To better understand adipose tissue
Adipose tissue consists of more than 99% of storage lipids, mainly triglycerides that are stored within the cell in so-called lipid droplets. Nonetheless, the remaining 0.5-1% of lipids are sufficient to build a metabolically active cell in all its complexity.

Despite the enormous importance of adipose tissue in human health and diseases (like diabetes), no standardized method existed so far, to quantitatively and reproducibly analyze its lipidome. Thus, Paul Langerhans Institute Dresden (PLID), German Center for Diabetes Research (DZD), the Institute for Clinical Chemistry and Laboratory Medicine of the University Hospital Carl Gustav Carus Dresden (IKL) and Lipotype GmbH chose to tackle this urgent need. Their joint vision of an omics-driven clinic, fueled the development of a shotgun lipidomics protocol for adipose tissue.


A new protocol
This new and validated protocol wants to facilitate the systematic molecular profiling of adipose tissue by providing high reproducibility and linear dynamic range for all lipid classes. Besides covering all types of adipose tissue, it can be used for fatty organs, and can be integrated with further omics approaches used in pre-clinical research.


Resources

Press Release: Dresden scientists develop new shotgun lipidomics method for molecular profiling of adipose tissue


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Lipidomics: A Rising Star in Omics Research

Technology Networks published a new introductory article on lipidomics last week. They spoke to Dr. Christian Klose about applications in the field of lipid research and to Henri Deda about LEA, the new Lipidomics Excellence Award.


The article in short
The article provides a brief introduction to the research field of lipids: lipidomics. Summarizing recent developments and challenges of the past, granting an overview on today’s lipidomics technology and discussing the broad field of lipidomics applications in detail, the article is a short and entertaining read. Dr Christian Klose, Head of Research and Development at Lipotype, comments on various aspects providing examples for current research and product developments in various industries and academia. To complete the picture of current developments in lipidomics, the motivation to found and organize the Lipidomics Excellence Award finishes off the article.


Lipidomics Excellence Award
LEA, the Lipidomics Excellence Award, has been created to promote, support and strengthen researchers who are eager to contribute to the progress of life sciences through lipidomics. Up to three individuals with ongoing research are awarded with comprehensive research prizes to support their projects. Applications are open to all researchers who are eager to strengthen life sciences through lipidomics. Call for applications is open till March 30, 2019.

LEA is supported by LIPID MAPS, SwissLipids and Lipotype; the media LABO, the Journal of Lipid Research and transkript aligned themselves with LEA too.


Resources

Technology Networks Article: Lipidomics – A Rising Star in “OMICS” Research
Press Release: Lipotype Launches first global Lipidomics Excellence Award


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Lipotype launches first global Lipidomics Excellence Award

Lipotype announces LEA, the Lipidomics Excellence Award, for breakthrough lipidomics projects. Call for applications is open till March 30, 2019.


LEA at a glance
LEA has been created to promote, support and strengthen researchers who are eager to contribute to the progress of life sciences through lipidomics.

Up to three individuals with ongoing research are awarded with comprehensive research prizes to support their projects. Applications are open to all researchers who are eager to strengthen life sciences through lipidomics.

The awardees are selected by a panel composed of internationally renown members of academia, each of them recognized as leading experts in their respective fields.

LEA is supported by LIPID MAPS, SwissLipids and Lipotype.


The first prize
The winner of the first prize will receive 55,000 EUR worth of analysis services in order to put their idea to test. The awardee will be presenting their research at an internationally leading experts summit for lipids and lipidomics, the EMBO Workshop “Lipid function in health and disease” in Dresden (Sept 27th – 30th, 2019). A press conference will be held to present the project and formally handover the LEA 2019 trophy.


How to apply
Individual researchers from academia and industry and their ongoing projects can apply for LEA 2019. Applicants are asked to outline their idea for a project or research approach whose results they think can be boosted by a detailed lipid analysis. All applications shall be submitted until March 30, 2019 via the online submission form.


Resources

Press Release: Lipotype Launches first global Lipidomics Excellence Award – ENG
Press Release: Lipotype startet den ersten weltweiten Lipidomics Excellence Award – DEU
Online Submission Form


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Dermal drug development for SLS associated ichthyosis

Lipotype put online a new biotech & dermatology customer reference with Aldeyra Therapeutics about lipid analysis for topical dermal drug development for the treatment of ichthyosis associated with SLS.


The project in short
Sjögren-Larsson Syndrome (SLS) is a rare inborn error of aldehyde metabolism characterized by severe skin thickening (ichthyosis), retinal disease, and neurological dysfunction. As of today, no therapy that addresses SLS has been approved. Aldeyra Therapeutics has conducted a Phase 2 randomized, parallel-group, double-blind, vehicle-controlled, multi-center clinical trial of topical dermal reproxalap for the treatment of ichthyosis associated with SLS. The results of the trial demonstrated clinically meaningful and statistically significant improvements of SLS skin symptoms of patients after only eight weeks of treatment. A multi-center Phase 3 clinical trial is ongoing.


What Lipotype did
Lipotype Shotgun Skin Lipidomics provided Aldeyra Therapeutics with lipid analysis of skin samples for identification of relevant lipid biomarkers in the Phase 2 clinical trial. Results of the skin lipidomics analysis delivered evidence for a correlation between clinical effects and those skin lipid biomarkers. Consistent with the clinical activity of reproxalap, significant dermal biomarker changes were noted in reproxalap-treated patients but not vehicle-treated patients. Cholesterol, which is significantly elevated in the skin of SLS patients, was reduced in reproxalap-treated patients more than in vehicle-treated patients.


About Aldeyra Therapeutics
Aldeyra Therapeutics is a biotechnology company devoted to improving lives by inventing, developing, and commercializing next-generation medicines that treat immune-mediated and metabolic diseases. Aldeyra’s lead product candidate, reproxalap (formerly called NS2), is a small molecule RASP (Reactive Aldehyde Species) inhibitor in Phase 3 clinical development for the treatment of dry eye disease, allergic conjunctivitis, noninfectious anterior uveitis, and Sjögren-Larsson syndrome. With its focus on a carefully selected range of diseases, Aldeyra Therapeutics is devoted to improving lives through outstanding innovation.


Find the full customer reference

Customer reference Aldeyra Therapeutics: lipid analysis for topical dermal drug development for the treatment of ichthyosis associated with SLS


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