Tag Clinical Trial

When to eat fatty meals: nutrition researchers discover new “biological lipid metabolism clock”

Just in time of Christmas, scientists from the German Institute for Human Nutrition (DIfE) and Lipotype GmbH have published their results of their research on the influence of fatty breakfasts and dinners on lipid metabolism. Their newly discovered “biological lipid metabolism clock” fills a gap in nutritional medicine to activate nutrition for prevention and intervention, and to research how specific foods at specific times of the day can contribute to our health or disease.


Two groups of scientists, one goal
The research group of PD Dr. Olga Ramich at the German Institute for Human Nutrition (DIfE) and the scientists of Lipotype GmbH share one mission: combat the diseases which plague modern society. Together, they want to activate nutrition and diet as a tool for prevention and intervention of widespread diseases such as diabetes.

Four years ago, during a meetup in Berlin, both agreed that the lack of molecular data about the influence of the diet on lipid metabolism was a black box of scientific mysteries. “In nutrition research, we had come to grips with general recommendations like less sugar and less fat.”, remembers Dr. Christian Klose from Lipotype GmbH, “But the questions we as a group of scientists wanted to answer were: are there foods with measurable health benefits and what happens with us if we eat fatty in the morning or in the evening?” The DIfE research group specialized in nutritional medicine developed a setup for a clinical trial to answer these questions.


A clinical study to answer these questions
In a first step, the metabolism of the health study participants was calibrated through a strict diet plan. After this period, one group of the study participants ate a fatty meal for breakfast and a carbohydrate-rich meal for dinner. The second group received the reversed meal plan. During this last step, blood samples were drawn from all participants before and after each meal.

“We wanted to understand how the lipid metabolism and its hundreds of different lipids in blood plasma react to our diet program.”, explains PD Dr. Olga Ramich from DIfE, “And, we were interested in how these changes in blood plasma lipid levels are linked to insulin sensitivity, which can be a great indicator to identify patients who are prone to developing diabetes.” The crux: traditional lipid analysis was not detailed enough to answer these questions. Which is why the samples were sent to Lipotype for a shotgun lipidomics analysis, a detailed molecular analysis of hundreds of lipids at once.


Lipidomics discovers a new biological clock
The extracted blood plasma lipids were shot into a mass spectrometer. Bioinformatics solutions unveiled 14 lipid classes with a total of 672 different lipids from the mass spectrometer results, and bio-statistical methods converted these into lipidomics charts and graphs. “We discovered a daily lipid metabolism pattern – a biological lipid metabolism clock. This clock responded significantly differently to same meals in the morning than in the evening, and such time-dependent pattern  was found for both high-carb and high-fat meals.”, states Dr. Christian Klose. Next, the lipidomics results were plotted against insulin sensitivity measurements to discover a link between 7 of the 14 lipid classes and insulin sensitivity.

“These results are fundamental to activate nutrition and diet as a tool for prevention and intervention of widespread diseases. It’s the basis to research which specific foods at specific time of the day can help adjust insulin sensitivity to healthy levels and act against diabetes.”, comments PD Dr. Olga Ramich, “Discovering the lipid metabolism clock underlines what our nutritional medicine research group has been emphasizing for years: the concept of an internal clock applies to our metabolism too. Living against this clock is unhealthy and increases the risk for diabetes.”


Resources

1 – Publication: Shotgun lipidomics discovered diurnal regulation of lipid metabolism linked to insulin sensitivity in non-diabetic men
2 – Press Release: The Biological Lipid Metabolism Clock
3 – Pressemitteilung: Die Biologische Fettstoffwechsel-Uhr


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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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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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Lipotype’s customer Lyomark Pharma announces partnership

Lyomark Pharma, a customer of Lipotype, announces a partnership with Aerogen Pharma to develop an inhaled surfactant for the treatment of preterm infants with Respiratory Distress Syndrome (RDS). At the same time clinical trials with the new delivery system have been initiated and the first patients have been recruited. Read more in the press release of Lyomark and Aerogen:


Read more in the press release of Lyomark and Aerogen here:
Aerogen Pharma and Lyomark Pharma partner to develop inhaled surfactant, begin a Phase 2 clinical trial