MRI reveals brain damage in obese teens
November 25, 2019
Science Daily/Radiological Society of North America
Researchers using MRI have found signs of damage that may be related to inflammation in the brains of obese adolescents, according to a study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).
Obesity in young people has become a significant public health problem. In the U.S., the percentage of children and adolescents affected by obesity has more than tripled since the 1970s, according to the Centers for Disease Control and Prevention. Data from the World Health Organization indicates that the number of overweight or obese infants and young children ages five years or younger increased from 32 million globally in 1990 to 41 million in 2016.
While obesity is primarily associated with weight gain, recent evidence suggests that the disease triggers inflammation in the nervous system that could damage important regions of the brain. Developments in MRI like diffusion tensor imaging (DTI), a technique that tracks the diffusion of water along the brain's signal-carrying white matter tracts, have enabled researchers to study this damage directly.
For the new study, researchers compared DTI results in 59 obese adolescents and 61 healthy adolescents, ages 12 to 16 years. From DTI, the researchers derived a measure called fractional anisotropy (FA), which correlates with the condition of the brain's white matter. A reduction in FA is indicative of increasing damage in the white matter.
The results showed a reduction of FA values in the obese adolescents in regions located in the corpus callosum, a bundle of nerve fibers that connects the left and right hemispheres of the brain. Decrease of FA was also found in the middle orbitofrontal gyrus, a brain region related to emotional control and the reward circuit. None of the brain regions in obese patients had increased FA.
"Brain changes found in obese adolescents related to important regions responsible for control of appetite, emotions and cognitive functions," said study co-author Pamela Bertolazzi, a biomedical scientist and Ph.D. student from the University of São Paulo in Brazil.
This pattern of damage correlated with some inflammatory markers like leptin, a hormone made by fat cells that helps regulate energy levels and fat stores. In some obese people, the brain does not respond to leptin, causing them to keep eating despite adequate or excessive fat stores. This condition, known as leptin resistance, makes the fat cells produce even more leptin.
Worsening condition of the white matter was also associated with levels of insulin, a hormone produced in the pancreas that helps regulate blood sugar levels. Obese people often suffer from insulin resistance, a state in which the body is resistant to the effects of the hormone.
"Our maps showed a positive correlation between brain changes and hormones such as leptin and insulin," Dr. Bertolazzi said. "Furthermore, we found a positive association with inflammatory markers, which leads us to believe in a process of neuroinflammation besides insulin and leptin resistance."
Dr. Bertolazzi noted that additional studies are needed to determine if this inflammation in young people with obesity is a consequence of the structural changes in the brain.
"In the future, we would like to repeat brain MRI in these adolescents after multi-professional treatment for weight loss to assess if the brain changes are reversible or not," she added.
https://www.sciencedaily.com/releases/2019/11/191125100405.htm
Only-children more likely to be obese than children with siblings
November 6, 2019
Science Daily/`Elsevier
Families with multiple children tend to make more healthy eating decisions than families with a single child.
A new study in the Journal of Nutrition Education and Behavior, published by Elsevier, found that only-children, who researchers refer to as "singletons," had less healthy family eating practices, beverage choices, and total Healthy Eating Index 2010 score, coming in lower on three out of the 12 areas measured. They also had significantly lower total scores across weekdays, weekends, and on average, indicating there are both individual and collective differences in eating patterns between the groups.
"Nutrition professionals must consider the influence of family and siblings to provide appropriate and tailored nutrition education for families of young children," said lead author Chelsea L. Kracht, PhD. Dr. Kracht completed the research during her PhD program alongside Dr. Susan Sisson at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. "Efforts to help all children and families establish healthy eating habits and practices must be encouraged."
Data was self-reported in daily food logs kept by mothers over the course of three days -- two weekdays and one weekend day. Teachers kept logs by proxy for any food children ate while at school. Mothers also completed the Family Nutrition and Physical Activity questionnaire to evaluate typical family eating behaviors like food and beverage choice.
Researchers found mothers of singleton children were more likely to be obese themselves. Moreover, maternal BMI had a much stronger connection to child BMI percentile and waist circumference percentile than singleton status. Maternal BMI did not significantly contribute to overall eating patterns but did contribute to empty calories.
The study only looked at mothers and children and so could not speak to the impact of fathers' eating patterns, but the results were independent of marital status.
The study also found that time spent in away-from-home care like school and daycare was not connected to children's eating patterns. This points to the difference coming from inside the household, including a difference in how frequently the family eats in front of the television (family eating practices score) and sugary drinks consumption (beverage choices score), which differed between groups in the study.
"Healthier eating behaviors and patterns may result from household-level changes rather than peer exposure, as peer exposure is also present in away-from-home care," Dr. Kracht said.
Dr. Kracht and her colleagues are continuing their research, looking specifically into household and family dynamics and how they influence children's eating behavior, physical activity, sleep, and other factors contributing to obesity.
https://www.sciencedaily.com/releases/2019/11/191106183102.htm
Glucose wears down circadian clocks in obesity, may drive cardiovascular risk
October 24, 2019
Science Daily/Medical College of Georgia at Augusta University
High glucose in obesity appears to gum up the works of the circadian clocks inside our cells that help regulate the timing of many body functions across the 24-hour day and drive the risk of cardiovascular disease, scientists say.
"We have demonstrated that glucose and cardiovascular problems are intrinsically linked in obesity," says Dr. David Stepp, vascular biologist in the Vascular Biology Center and Leon Henri Charbonnier Endowed Chair in Physiology at the Medical College of Georgia at Augusta University.
"We have also demonstrated that high glucose impairs circadian clock function. Now we want to know if we fix the clock, do we fix the cardiovascular problems," says Stepp.
He and Dr. David Fulton, director of the Vascular Biology Center and Regents professor in the MCG Department of Pharmacology and Toxicology, are principal investigators on a $2.7 million grant from the National Institutes of Health that is enabling the use of intermittent fasting and a developing category of clock repair drugs to find the answer.
Circadian clocks set the rhythm of our bodies so that we eat, sleep and wake at the right time. What is less well recognized is the important role of circadian clocks in anticipating these events and preparing our organs and cells so they function optimally at the right time as well as anticipating when to rest and rejuvenate, says Fulton.
"Every cell in your body has a clock in it that is used to anticipate daily needs," says Fulton, your blood pressure and heart rate drop at nighttime and surge in the morning when your feet hit the ground and blood must fight against gravity.
"Your metabolic needs at night are different than your metabolic needs when you are awake," says Stepp. "Some of them are more; some of them are just different."
Sleep is supposed to be a period of rest and recovery for each of our cells just like it is for us overall. "You are doing regeneration, you are doing restoration, you are doing repair," Stepp says. At daybreak, genes active at night should be turned off, and genes important for daily activities should be turned on and our metabolism should switch from a restorative to active phase.
Blood flow adjusts to match these dynamic metabolic needs, and our circadian clocks are sort of intermediaries between metabolism and our cardiovascular system that coordinate changes in metabolism with changes in cardiovascular gene function.
The MCG scientists have evidence that obesity can break these links between metabolism and cardiovascular regulation. Excessive food consumption, particularly foods that are high in sugar and carbohydrates, some of which our body also breaks down into glucose, dampens clock function and imperils cardiovascular health. "It's certainly an accelerant," Fulton says of high glucose.
They have documented both high glucose levels and significant circadian dysfunction in a mouse model of hyperphagia. These obese mice have tremendous appetites, high glucose and high blood pressure that does not dip at night when it should, and most importantly, dysfunction of the single layer of endothelial cells that line blood vessels. Normally endothelial cells provide a smooth surface for blood to pass over and play a key role in enabling blood vessels to dilate in response to greater blood volume so blood pressure doesn't increase too much.
Endothelial dysfunction, a focus of their cardiovascular studies, is a major initiator of atherosclerosis, and what many of us think of as heart disease. Dysfunctional endothelial cells become inflamed, sticky and produce more damaging reactive oxygen species and less nitric oxide, which impairs blood vessel dilation. The result can be a tortuous passageway for blood, sticky walls where cells pile up and coronary artery disease.
When the MCG scientists disrupt the gears of circadian clocks in mice using genetic approaches or environmental modifications, including jet lag light cycles, both approaches result in loss of clock function and increase the risk of endothelial dysfunction and disease. Now Fulton and Stepp want to know more about how the clocks lose timing and how best to intervene.
They have bred the obese mice with a clock reporter, a gear of the circadian clock linked to a fluorescent protein that lights up when the gear is turned, so they can better track clock activity.
Using these clock reporter mice, they saw huge downturns in circadian rhythms and clock-related genes in obese mice and high levels of glucose in the blood upstream of these events.
"The first thing we want to know is can we understand why the clock is rundown in obesity," says Stepp. "The second thing is what mediates the effects of circadian disruption on cardiovascular disease, and if we fix that disruption, get the amplitude back up, does it fix the cardiovascular problems."
If intermittent fasting, which should help restore the normal peaks and valleys of glucose levels, or the clock-fixer drugs they are using for these studies interfere with progression to cardiovascular problems, they should have some answers.
They and others already have evidence that the small, clock-fixer molecule they are using, nobiletin, enhances the amplitude of and reverses the reduction of clock function in obesity. Whether or not that improves cardiovascular function, is one of the things they want to learn more about now.
That includes checking whether high glucose and resulting clock dysfunction work through the increased expression of galectin-3, a receptor associated with cardiovascular disease that they have seen in their mouse model, to produce expression of the gene NOX1, which converts oxygen to damaging super oxide, in endothelial cells.
They still are not certain which clock(s) are most central to this problem. Everywhere they have looked -- heart, kidney, liver, blood vessels and endothelial cells -- they have seen these rundown clocks. For now they are focusing on clocks in the endothelial cells, where they think a lot of the problems start. They don't expect to identify a specific clock(s) in these studies, but if their findings continue to hold they will start knocking out clocks in other cells in future studies.
They think the problem quite literally is about timing, says Fulton. Proper signaling requires a peak and trough and constant overstimulation by too much glucose has the body instead trying to turn clocks off.
The scientists note that if you have a healthy musculature despite obesity, it mitigates, at least for a time, the impact of high glucose on the vasculature. Muscle is a first and fast user of glucose, quickly pulling it out of the circulation. "If it goes into the muscle, it never comes out again," says Stepp. "It gets used or stored for later." Obese mice, like humans, lose muscle mass. In some of their initial studies, they preserved muscle mass in obese mice, which also prevented cardiovascular damage.
They note that both aging, when muscle naturally loses volume even in individuals who remain active, and spinal cord injuries or other conditions that leave us immobile, have some of the same cardiovascular risks as obesity.
While circadian-related cardiovascular risk also is heightened by lifelike scenarios like shiftwork or chronic jet lag in even a lean mouse, it is way worse for an obese one, Stepp says.
Adult obesity results from factors that include consuming more calories than are expended, medications and other exposures as well as genetics, including gene variants that increase hunger and food intake, according to the Centers for Disease Control and Prevention. It is associated with poorer mental health, reduced quality of life and contributes to the leading causes of death in the United States including diabetes, heart disease, stroke and some types of cancer. Obesity itself is considered a major risk factor for cardiovascular disease, and a major risk as well for diabetes and high blood pressure, which are other top cardiovascular risks.
https://www.sciencedaily.com/releases/2019/10/191024093602.htm
Evidence of behavioral, biological similarities between compulsive overeating and addiction
October 17, 2019
Science Daily/Boston University School of Medicine
Does yo-yo dieting drive compulsive eating? There may be a connection.
According to Boston University School of Medicine (BUSM) researchers the chronic cyclic pattern of overeating followed by undereating, reduces the brain's ability to feel reward and may drive compulsive eating. This finding suggests that future research into treatment of compulsive eating behavior should focus on rebalancing the mesolimbic dopamine system -- the part of the brain responsible for feeling reward or pleasure.
An estimated 15 million people compulsively eat in the U.S. It is a common feature of obesity and eating disorders, most notably, binge eating disorder. People often overeat because it is pleasurable in the short term, but then attempt to compensate by dieting, reducing calorie intake and limiting themselves to "safe," less palatable food. However, diets often fail, causing frequent "relapse" to overeating of foods high in fat and sugar (palatable foods).
"We are just now beginning to understand the addictive-like properties of food and how repeated overconsumption of high sugar -- similar to taking drugs -- may affect our brains and cause compulsive behaviors," said corresponding author Pietro Cottone, PhD, associate professor of pharmacology & experimental therapeutics at BUSM and co-director of the Laboratory of Addictive Disorders.
In order to better understand compulsive and uncontrollable eating, Cottone and his team performed a series of experiments on two experimental models: one group received a high sugar chocolate-flavored diet for two days each week and a standard control diet the remaining days of the week (cycled group), while the other group, received the control diet all of the time (control group).
The group that cycled between the palatable food and the less palatable, spontaneously developed compulsive, binge eating on the sweet food and refused to eat regular food. Both groups were then injected with a psychostimulant amphetamine, a drug that releases dopamine and produces reward, and their behavior in a battery of behavioral tests was then observed.
While the control group predictably became very hyperactive after receiving amphetamine, the cycled group did not. Furthermore, in a test of the conditioning properties of amphetamine, the control group was attracted to environments where they previously received amphetamine, whereas the cycled group were not. Finally, when measuring the effects of amphetamine while directly stimulating the brain reward circuit, the control group was responsive to amphetamine, while the cycled group was not.
After investigating the biochemical and molecular properties of the mesolimbic dopamine system of both groups, the researchers determined that the cycled group had less dopamine overall, released less dopamine in response to amphetamine and had dysfunctional dopamine transporters (protein that carries dopamine back into brain cells) due to deficits in their mesolimbic dopamine system.
"We found that the cycled group display similar behavioral and neurobiological changes observed in drug addiction: specifically, a "crash" in the brain reward system," explained Cottone. "This study adds to our understanding of the neurobiology of compulsive eating behavior. Compulsive eating may derive from the reduced ability to feel reward. These findings also provide support to the theory that compulsive eating has similarities to drug addiction."
"Our data suggest that a chronic cyclic pattern of overeating will reduce the brain's ability to feel reward -- feeling satiated. This results in a vicious circle, where diminished reward sensitivity may in turn be driving further compulsive eating," said lead author Catherine (Cassie) Moore, PhD, former graduate student in the Laboratory of Addictive Disorders at BUSM.
The researchers hope these findings spark new avenues of research into compulsive eating that will lead to more effective treatments for obesity and eating disorders.
https://www.sciencedaily.com/releases/2019/10/191017125240.htm