(Press-News.org) Researchers at the Karolinska Institutet, University of Oxford and University of Copenhagen have shown that elevated levels of lipids known as ceramides can be associated with a ten-fold higher risk of death from cardiovascular disease. Treatment with liraglutide could keep the ceramide levels in check, compared with placebo. The results have been published in the Journal of the American College of Cardiology.
Approximately 16 percent of the Swedish population suffers from obesity (BMI over 30), which is one of the greatest risk factors for cardiovascular diseases such as myocardial infarction and stroke. The World Health Organisation (WHO) estimates that cardiovascular diseases are the main cause of mortality worldwide, with more than 17 million deaths a year.
"Understanding the link between obesity and cardiovascular diseases is important and can lead the way to the development of new therapies," says principal investigator docent Craig Wheelock at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet.
Fat has traditionally been seen as simply storage tissue, but in recent years it has been shown to be a 'biochemical laboratory' capable of producing signalling molecules that exert potent biological functions. Understanding how adipocytes produce and release these molecules opens the possibility of reprogramming them with the aim of preventing future incidence of cardiovascular disease.
Applying a mass-spectrometry method called metabolomics, the Wheelock Laboratory was able to measure levels of multiple metabolites secreted by two kinds of human fat tissue.
The fat that accumulates around the heart in obese individuals secreted different metabolites relative to subcutaneous fat. Notably, thoracic adipose tissue (which surrounds the heart) from obese individuals secreted higher levels of ceramides, a kind of lipid that belongs to the sphingolipid family. In particular, elevated levels were observed of a lipid variant called C16:0-ceramide, which is based on palmitic acid - a saturated fat consisting of 16 carbon atoms. Ceramides are found in high levels in cell membranes and are also important signalling molecules.
The researchers were also able to show that ceramides secreted from adipose tissue damaged human blood vessels by initiating a process called oxidative stress, which can eventually lead to heart attacks and stroke.
"These results show emphatically that fat is not just energy-storage tissue but also a source of important bioactive molecules that can have powerful immunomodulatory functions," Wheelock says. "In addition, all tissue is not equal, and the type of fat is clearly important in determining the observed biological function."
To understand the significance of the cardiovascular effects of the ceramides, the researchers studied 633 patients with atherosclerosis, who were monitored for more than five years. They found that elevated levels of both C16:0-ceramide and its glycosylated variant could be linked to a ten-fold increase in the risk of fatal cardiovascular disease, even after controlling for other risk factors including age and weight. The results were consistent with earlier studies by other research groups.
"The results suggest that it could be worth incorporating the measurement of different kinds of sphingolipids, both in their original form as well as the glycosylated variants, to better gauge the risk of the occurrence of a fatal cardiovascular event," says co-author Antonio Checa, researcher at Karolinska Institutet who developed the sphingolipid platform and conducted the analyses.
The results also gave the researchers reason to examine if high ceramide levels in the blood can be effectively reduced. In the last part of the study, 32 volunteers were placed on a low-calorie diet for eight weeks before being split into two groups, one that received a placebo and one that received liraglutide, a GLP 1-analogue drug that is approved for the treatment of obesity and type 2 diabetes. Both groups continued the low-calorie diet for another 44 weeks. One year after the study onset, ceramide levels in the blood had increased significantly in the control group, while levels remained stable in the liraglutide group.
"The most important findings are that we add to the evidence that there is a direct correlation between risk of fatal cardiovascular disease and ceramide levels in the blood, and that this can be treated with an existing medication," Wheelock says.
The study was led and coordinated by Professor Charalambos Antoniades at the University of Oxford.
"We reveal for the first time the role that the ceramides play as messengers that bring about the damaging effect on blood vessels that we see in obesity," Charalambos Antoniades says. "This presents unique opportunities for the improved diagnosis and treatment of cardiovascular disease."
INFORMATION:
The study was financed by the Swedish Heart and Lung Foundation, the Novo Nordisk Foundation and the British Heart Foundation.
Publication: "Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease," Nadia Akawi, Antonio Checa, Alexios S. Antonopoulos, Ioannis Akoumianakis, Evangelia Daskalaki, Christos P. Kotanidis, Hidekazu Kondo, Kirsten Lee, Dilan Yesilyurt, Ileana Badi, Murray Polkinghorne, Naveed Akbar, Julie Lundgren, Surawee Chuaiphichai, Robin Choudhury, Stefan Neubauer, Keith M. Channon, Signe S. Torekov, Craig E. Wheelock and Charalambos Antoniades. Journal of American College of Cardiology, online May 24, 2021, doi: 10.1016/j.jacc.2021.03.314
Has your heart ever started to race at the thought of an upcoming deadline for work? Or has the sight of an unknown object in a dark room made you jump? Well, you can probably thank your amygdala for that.
The small almond-shaped brain structure is central to how we perceive and process fear. As we start to learn to associate fear with cues in our environment, neuronal connections within the amygdala are dynamically altered in a process called synaptic plasticity. Although this physiological mechanism is important for facilitating fear learning, it has mostly been studied in the context of excitatory neurons within the amygdala. Far less is known about the role inhibitory cells ...
CHICAGO, May 24, 2021--More than a year after COVID-19 appeared in the U.S., dentists continue to have a lower infection rate than other front-line health professionals, such as nurses and physicians, according to a study published online ahead of the June print issue in the Journal of the American Dental Association. The study, "COVID19 among Dentists in the U.S. and Associated Infection Control: a six-month longitudinal study," is based on data collected June 9 - Nov. 13, 2020.
According to the study, based on the number of dentists with confirmed or probable COVID-19 infections over more than six months, the cumulative infection rate for U.S. dentists is 2.6%. The monthly incidence ...
Researchers at Lund University in Sweden have developed an algorithm that combines data from a simple blood test and brief memory tests, to predict with great accuracy who will develop Alzheimer's disease in the future. The findings are published in Nature Medicine.
Approximately 20-30% of patients with Alzheimer's disease are wrongly diagnosed within specialist healthcare, and diagnostic work-up is even more difficult in primary care. Accuracy can be significantly improved by measuring the proteins tau and beta-amyloid via a spinal fluid sample, or PET scan. However, those methods are expensive and only available at a relatively few specialized memory clinics worldwide. Early and accurate ...
Ecology, the field of biology devoted to the study of organisms and their natural environments, needs to account for the historical legacy of colonialism that has shaped people and the natural world, researchers argued in a new perspective in the journal Nature Ecology & Evolution.
To make ecology more inclusive of the world's diverse people and cultures living in diverse ecosystems, researchers from University of Cape Town, North West University in South Africa and North Carolina State University proposed five strategies to untangle the impacts of colonialism on research and thinking in the field today.
"There are significant biases in our understanding ...
The neural representation of a familiar face strengthens faster when you see someone in person, according to a new study published in JNeurosci.
The brain loves faces -- there's even an interconnected network of brain areas dedicated to face-processing. Despite all the research on how the brain sees faces, little is known about how the neural representation of a face changes as it becomes familiar.
To track how familiarity brain signals change, Ambrus et al. measured participants' brain activity with EEG before and after getting to know different ...
A strange phenomenon happens with modern blue whales, humpback whales and gray whales: they have teeth in the womb but are born toothless. Replacing the teeth is baleen, a series of plates composed of thin, hair- and fingernail-like structures growing from the roof of their mouths that act as a sieve for filter feeding small fish and tiny shrimp-like krill.
The disappearing embryonic teeth are testament to an evolutionary history from ancient whales that had teeth and consumed larger prey. Modern baleen whales on the other hand use their fringed baleen to strain their miniscule prey from water, hence the term filter feeding.
A new study that utilized high-resolution computed tomography (CT) to ...
East Hanover, NJ. May 24, 2021. A recent qualitative study of rehabilitation professionals caring for people with spatial neglect enabled researchers to identify interventions to improve rehabilitation outcomes. Experts reported that implementation of spatial neglect care depends on interventions involving family support and training, promotion of interdisciplinary collaboration, development of interprofessional vocabulary, and continuous treatment and follow-up assessment through care transitions.
The article, "Barriers and Facilitators to Rehabilitation Care of Individuals with Spatial ...
Scientists at the University of York have made significant progress in the development of a nasal spray treatment for patients with Parkinson's disease.
Researchers have developed a new gel that can adhere to tissue inside the nose alongside the drug levodopa, helping deliver treatment directly to the brain.
Levodopa is converted to dopamine in the brain, which makes-up for the deficit of dopamine-producing cells in Parkinson's patients, and helps treat the symptoms of the disease. Over extended periods of time, however, levodopa becomes less effective, and increased doses are needed.
Professor David Smith, from the ...
Extra funding should be made available for early years care in the wake of the pandemic, researchers say.
Experts at the University of Leeds, University of Oxford and Oxford Brookes University have made the call after assessing the benefits of early childhood education and care (ECEC) for children under three during COVID-19.
They found children who attended childcare outside the home throughout the first UK lockdown made greater gains in language and thinking skills, particularly if they were from less advantaged backgrounds.
And now they are making several policy recommendations ...
Research Study Key Takeaways:
Ridesharing can reduce a passenger's risk of being a target of sexual assault by providing a more reliable and timely transportation option for traveling to a safer place.
The entry of Uber into a city contributes to a 6.3% reduction in rape incidents.
A 1% increase in Uber pickups in a neighborhood translates to a more than 3% decrease in the likelihood of sexual assaults.
CATONSVILLE, MD, May 24, 2021 - Contrary to portraits painted in popular media, new research involving ridesharing services shows they provide an additional level of protection for potential sexual assault victims, particularly ...
