Breaking News
January 18, 2019 - New study shows link between secondhand smoke and cardiac arrhythmia
January 18, 2019 - DZIF scientists reveal problems with available diagnostics for Zika and chikungunya virus
January 18, 2019 - Breast cancers more likely to metastasize in young women within 10 years of giving birth
January 18, 2019 - Blood vessels can now be created perfectly in a petri dish
January 18, 2019 - Study identifies prominent socioeconomic and racial disparities in health behavior in Indiana
January 18, 2019 - Young-Onset Type 2 Diabetes Tied to Increased Hospitalization Risk
January 18, 2019 - For-profit nursing schools associated with lower performance on nurse licensure test
January 18, 2019 - Considering the culture of consent in medicine
January 18, 2019 - Researchers identify comprehensive guidelines for managing severe atopic dermatitis
January 18, 2019 - Analyzing proteins in blister fluid may classify burn severity more accurately
January 18, 2019 - Study finds higher suicide rates among youth who were Medicaid enrollees
January 18, 2019 - Opioid drugs often overprescribed to children for pain relief, say CHOP surgeons
January 18, 2019 - New biodegradable wound dressing material accelerates healing
January 18, 2019 - Life in Space May Take Toll on Spinal Muscles
January 18, 2019 - Bulldogs’ screw tails linked to human genetic disease
January 18, 2019 - Immunotherapy target identified for pediatric cancers
January 18, 2019 - Financial stress may increase heart disease risk in African Americans
January 18, 2019 - Scientists solve another piece of Ebola virus puzzle
January 18, 2019 - New project finds how endocrine disruptors interfere with thyroid functions
January 18, 2019 - Research finds decline in ketone body utilization when coronary circulation is reduced
January 18, 2019 - Let’s map our DNA and save billions each year in health costs
January 18, 2019 - AI demonstrates potential to identify irregular heart rhythms as well as humans
January 17, 2019 - Study shows link between air pollution and increased risk of sleep apnea
January 17, 2019 - Neck-strengthening exercises can protect athletes from concussions
January 17, 2019 - Computer model shows how to better control MRSA outbreaks
January 17, 2019 - Pain is unpleasant, and now scientists have identified the set of responsible neurons
January 17, 2019 - CUIMC Celebrates 2018-2019
January 17, 2019 - Study reveals potential pathway for endothelial cells to avoid apoptosis
January 17, 2019 - Hamilton Storage launches LabElite DeCapper SL to expand LabElite product family
January 17, 2019 - Location of epigenetic changes co-locate with genetic signal causing psychartric disorder
January 17, 2019 - Researchers awarded 6.1 million euros to address female fertility problems
January 17, 2019 - Counseling appointments fail to reduce weight gain during pregnancy, shows study
January 17, 2019 - Contraceptive patch that could provide 6 months of contraception within seconds
January 17, 2019 - Yeast model may pave way for development of novel therapies for metabolic disorders
January 17, 2019 - Study determines impact of antibiotic perturbation of the gut microbiome on skeletal health
January 17, 2019 - Cardiometabolic Risk Up With Tourette, Chronic Tic Disorder
January 17, 2019 - Hong Kong scientists claim ‘broad-spectrum’ antiviral breakthrough
January 17, 2019 - Researchers discover the brain cells that make pain unpleasant | News Center
January 17, 2019 - Hepatitis Is Common in New Cancer Patients
January 17, 2019 - Podcast: KHN’s ‘What The Health?’ Drug Prices Are Rising Again. Is Someone Going To Do Something About It?
January 17, 2019 - Smoking significantly increases your biological age, study shows
January 17, 2019 - B-group vitamins may be beneficial for people with first episode psychosis
January 17, 2019 - Researchers demonstrate how manganese produces parkinsonian syndrome
January 17, 2019 - Researchers suggest link between personality type and attitude towards others’ bodies
January 17, 2019 - Mutant mice administered with cocaine failed to exhibit hyperactivity, shows study
January 17, 2019 - Health Tip: Understanding a Heart Murmur
January 17, 2019 - Gut protein mutations shield against spikes in glucose
January 17, 2019 - Engineered immune cells target broad range of pediatric solid tumors in mice | News Center
January 17, 2019 - Study provides comprehensive description of associations between mental disorders
January 17, 2019 - Study finds link between high pesticide exposure and poor sense of smell among farmers
January 17, 2019 - Many cancer patients have undiagnosed hepatitis
January 17, 2019 - New study finds only 13% of outpatient antibiotic prescriptions to be appropriate
January 17, 2019 - Stem cell-based approach to diabetes offers hope for treatment
January 17, 2019 - New project receives €8.65 million from EU and Canada to ease genomic, health data sharing
January 17, 2019 - Improvements in pharmacological study to fight cognitive impairment in schizophrenia
January 17, 2019 - Study looks at trends over time in oral antibiotic prescribing by dermatologists
January 17, 2019 - Most substance use disorder treatment facilities do not offer medication treatment
January 17, 2019 - Multiple sclerosis could benefit from stem cell therapy
January 17, 2019 - Researchers manipulate T cells to improve transplant success
January 17, 2019 - Put away your rulers and reach for your phone
January 17, 2019 - Mindfulness linked with fewer menopausal symptoms
January 17, 2019 - Integrated care to women with PMADs offered at several levels
January 17, 2019 - Researchers identify MANF as a rejuvenating factor in parabiosis
January 17, 2019 - Truncal mutations study suggests new direction in origins of cancer
January 17, 2019 - Beckman Coulter launches new ClearLLab 10C System for clinical flow cytometry lab
January 17, 2019 - Effects of linoleic acid on the body are largely dependent on genes, shows study
January 17, 2019 - Pre-injury exercise reduces damage to both muscles and nerves, study finds
January 17, 2019 - Minimizing Antibody Size to Maximize Research Potential
January 17, 2019 - Research finds large genome in tiny forest defoliator
January 17, 2019 - Technology helps reduce the yearning for unhealthy food
January 17, 2019 - Imec develops prototype cardiovascular device
January 17, 2019 - New Drug Application for Insomnia Disorder Treatment Lemborexant Submitted in the United States
January 17, 2019 - What you should know about teeth whitening
January 17, 2019 - Why Older Adults Should Eat More Protein (And Not Overdo Protein Shakes)
January 17, 2019 - Colorectal cancer mortality rates predicted to increase globally
January 17, 2019 - Scientists discover mutational signatures of tumor hypoxia
January 17, 2019 - New evidence shows how fever alters immune cells
January 17, 2019 - Researchers find new class of blood pressure-regulating peptides in vampire bat venom
January 17, 2019 - Promega to exhibit new Maxwell RSC48 platform at 2019 Festival of Genomics
January 17, 2019 - Study pinpoints immune cells that could be key to tackling hypertension
Study finds excess fat disrupts heart cell’s energy system

Study finds excess fat disrupts heart cell’s energy system

image_pdfDownload PDFimage_print
The image shows mitochondria from normal heart (left) and lipid overloaded heart (right). Excess fat results in more numerous, more contorted mitochondria. These misshapen mitochondria do not produce energy as efficiently as normal mitochondria and, thus, lipid overload disrupts the heart’s energy-production system and may contribute to the two- to five-fold increased risk of heart failure in people with diabetes. Credit: E. Dale Abel Lab, University of Iowa

A University of Iowa study has identified how excess fat in the heart, a common feature in diabetes and obesity, can harm the cells’ essential ability to produce energy. Researchers believe the mechanism may contribute to the two- to five-fold increased risk of heart failure in people with diabetes.

The heart is the most energy-hungry organ in the body. Just like a combustion engine burning fuel to power the pistons, healthy heart cells consume fuel molecules to create the necessary energy to keep the heart pumping. This essential energy production takes place inside mitochondria, the self-contained “powerplant” organelles inside cells.

Although mitochondria in a healthy heart primarily use fatty acids as fuel, they can easily adapt to use other fuel molecules as needed, including glucose, lactate, and ketone bodies. Diabetes, however, reduces the heart muscle’s metabolic adaptability and causes heart cells to overuse fat as a metabolic fuel.

The study, published in Circulation Research, found that this cardiac lipid overload leads to numerous small, misshapen mitochondria that don’t produce energy as efficiently as normal mitochondria. Previous research from the UI team has suggested that problems with mitochondrial energy production may play a role in heart failure associated with diabetes.

“Diabetes, which affects almost 30 million Americans, significantly increases the risk of heart failure, and one of the cardinal manifestations of the hearts of people with diabetes is the tendency to overuse fat as a metabolic fuel, which ultimately leads to mitochondrial and cardiac damage,” explains study leader E. Dale Abel, MD, PhD, professor and departmental executive officer of internal medicine at the UI Carver College of Medicine and director of the Fraternal Order of Eagles Diabetes Research Center at the UI. “We have demonstrated and detected how increasing the amount of fat (lipid) that the heart consumes leads to dramatic changes in the structure and function of the mitochondria in the heart. These studies provide a new window into how these changes to mitochondria could occur in the lipid-overloaded heart.”

The UI team used genetically modified mice that mimic the increased fatty acid uptake (lipid overload) that characterizes diabetes to investigate the consequences of cardiac lipid overload on mitochondria. A novel 3-D electron microscopic cellular imaging technique developed by colleagues in Germany allowed the researchers to directly observe the structural changes to the mitochondria – rather like putting on a virtual reality headset inside the cardiac muscle cell, says Abel. In the mouse model, lipid uptake to heart is doubled. This modest increase resulted in mitochondria that became thinner and more twisted than mitochondria in healthy heart cells. These structural changes (almost like a noodle snaking through the heart) lead to an appearance of mitochondrial fragmentation when imaged by conventional electron microscopy.

The study also revealed the molecular cause of the change in mitochondrial structure. Prolonged lipid overload leads to increased levels of damaging substances called reactive oxygen species (ROS). The excess ROS disrupts the mitochondrial network by altering the activity of several important proteins that help control the size and shape of mitochondria.

Removing the excess ROS by overexpressing a molecule that helps “mop up” ROS molecules restored normal-looking mitochondria, which worked properly, despite the lipid overload.

Surprisingly, using the same approach to remove ROS in normal heart cells led to mitochondria that were four times as large as normal, suggesting that ROS levels are inversely proportional to mitochondria size.

The findings suggest that cardiac lipid overload disrupts normal mitochondrial structure, which may impair energy production and compromise heart function.


Explore further:
Mitochondrial protein in cardiac muscle cells linked to heart failure, study finds

More information:
Kensuke Tsushima et al, Mitochondrial Reactive Oxygen Species in Lipotoxic Hearts Induce Post-Translational Modifications of AKAP121, DRP1, and OPA1 That Promote Mitochondrial FissionNovelty and Significance, Circulation Research (2017). DOI: 10.1161/CIRCRESAHA.117.311307

Journal reference:
Circulation Research

Provided by:
University of Iowa

Tagged with:

About author

Related Articles