Single workout can boost metabolism for days: Study offers insight into brain’s potential role in fitness, diabetes therapy

Lounging around all weekend may weigh heavy on the minds of the health conscious. But these sedentary stretches may not affect the waistline, provided they’re preceded by a bit of exercise.

A new study from UT Southwestern Medical Center shows neurons in mice that influence metabolism are active for up to two days after a single workout. The research offers new insight into the brain’s potential role in fitness and — in the longer term — may provide a target for developing therapies that improve metabolism.

“It doesn’t take much exercise to alter the activity of these neurons,” said Dr. Kevin Williams, a neuroscientist at UT Southwestern. “Based on our results, we would predict that getting out and exercising even once in a semi-intense manner can reap benefits that can last for days, in particular with respect to glucose metabolism.”

The study, published in the December edition of Molecular Metabolism, measured the effects of short- and long-term exercise on two types of neurons that comprise the melanocortin brain circuit, which is shared by both humans and mice. One of the neuron types (POMC) is associated with reduced appetite, lower blood glucose levels, and higher energy burning when activated; the other type (NPY/AgRP) increases appetite and diminishes metabolism when activated.

The study found that a single bout of exercise can boost the activity of POMC neurons and inhibit the counterpart NPY/AgRP neuron for up to two days. Those changes last longer with more training.

The findings expand the scientific understanding of the melanocortin circuit, which previous studies showed could be altered through feeding or fasting but had not yet been linked to exercise.

The results also provide another avenue to research potential treatments to improve glucose metabolism in patients with conditions such as diabetes. More than 30 million Americans have diabetes, accounting for nearly 10 percent of the population. Another 84 million have prediabetes, which can lead to diabetes within five years, according to the Centers for Disease Control and Prevention.

“It is possible that activating melanocortin neurons may hold therapeutic benefits for patients one day, especially for diabetics who need improved blood-glucose regulation,” Dr. Williams said.

The study measured brain circuit activity in mice given training regiments that lasted from zero to 10 days. Scientists found that a single workout (consisting of three 20-minute treadmill runs) caused a decrease in appetite that lasted up to six hours. “This result may explain at the neural circuit level why many people don’t feel hungry immediately after exercise,” Dr. Williams said.

The longer-term effects of exercise were seen in the POMC neurons, which improve glucose metabolism when activated. These neurons remained active longer if they also expressed a protein called the leptin receptor.

Dr. Williams’ lab is preparing a second study to establish the mechanisms by which exercise triggers changes in melanocortin neurons. The planned study will also record more data on how those changes correlate with biological functions such as glucose metabolism and energy balance.

“This research is not just for improving fitness,” Dr. Williams said. “A better understanding of neural links to exercise can potentially help a number of conditions affected by glucose regulation.”

Source: Read Full Article

Discovery of the first common genetic risk factors for ADHD: Important step in understanding biological underpinnings of ADHD

A global team of researchers has found the first common genetic risk factors associated with attention deficit hyperactivity disorder (ADHD), a complex condition affecting around 1 in 20 children.

Professor Anita Thapar, from Cardiff University, who leads an ADHD research group as part of the Psychiatric Genomics Consortium, said: “This study marks a very important step in beginning to understand the genetic and biological underpinnings of ADHD.

“The genetic risk variants related to this condition play a significant role in brain-related and other core biological processes. The next step is to determine the exact role of these genes in ADHD to help us inform better treatments to support those affected by the condition.”

The team analysed genetic information from over 20,000 people affected with ADHD and over 35,000 people without the condition, the largest genetic study of ADHD to date.

Dr Joanna Martin, a research associate based at Cardiff University’s MRC Centre for Neuropsychiatric Genetics and Genomics, said: “We identified 12 genomic regions at which people with ADHD differed compared to unaffected individuals, and several of these regions are in or near genes with a known relationship to biological processes involved in healthy brain development.”

Further analyses showed that genetic risk for ADHD is shared with risk for other psychiatric and physical disorders, including depression, obesity, type 2 diabetes and lower levels of “good” HDL cholesterol.

The researchers also found that diagnosed ADHD appears to share much of the same genetic background as the traits of ADHD, like inattention and fidgetiness, that can be measured in the general population.

Working with the Early Genetics and Lifecourse Epidemiology Consortium (EAGLE), and researchers at Queensland Institute of Medical Research (QIMR), they compared the genetic risk for diagnosed ADHD with genetic markers associated with traits of ADHD in over 20,000 children and found a high correlation between the two, at around 97%.

“The correlation between these rather different definitions of ADHD suggests that clinically diagnosed ADHD may be the severe end of a continuous distribution of symptoms in the general population,” explained Dr Martin.

The collaboration consisted of European, North American and Chinese research groups that are part of the Psychiatric Genomics Consortium (PGC), as well as researchers from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) in Denmark.

Professor Anita Thapar said: “This is a landmark study because it involves patients from all over the world. This large number of patient samples has been lacking for ADHD, meaning our understanding of ADHD genetics has lagged behind physical disorders and other psychiatric disorders like schizophrenia and depression. Thanks in large part to Denmark, this is beginning to change.

“Every person with ADHD who has participated in research is making a real difference to advancing our understanding of the condition, and we hope this study leads to higher levels of participation and a greater interest from the UK in supporting ADHD research.”

Although the 12 genomic signals identified in this study are important, they capture only a very small amount of the risk for ADHD. Collectively, common genetic factors accounted for approximately 22% of the risk of ADHD. The role of other sources of genetic risk, for example, rarer genetic changes, as well as environmental factors will also be important to examine in future research studies.

Source: Read Full Article

New marker provides insights into the development of type 2 diabetes

Small chemical changes in the DNA building blocks, which may be influenceable by lifestyle factors, can reduce the amount of IGFBP2. A DIfE / DZD research team has now reported in the journal Diabetes that these epigenetic changes increase the risk of type 2 diabetes. Moreover, people with high blood levels of the binding protein IGFBP2 are less likely to develop this metabolic disorder. The changes in the blood are already detectable a few years prior to the onset of the disease.

According to the German Diabetes Health Report 2018, more than 5.7 million people in Germany suffer from type 2 diabetes. The affected individuals react inadequately to the hormone insulin, which leads to elevated blood glucose levels. This in turn can lead to strokes, heart attacks, retinal damage, kidney damage and nerve disorders. Since the metabolic disease develops gradually, initial damage has usually already occurred at the time of diagnosis. “In the future, our findings may help to identify risk potentials for type 2 diabetes even earlier and help to counteract the disease with preventive measures,” said Professor Annette Schürmann, head of the Department of Experimental Diabetology at the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) and speaker of the German Center for Diabetes Research (DZD).

Uncovering the molecular mechanisms

In addition to insulin, insulin-like growth factor 1 (IGF-1) is also involved in the metabolism of sugar and fat. The effect of this growth factor is weakened by binding to the IGF-binding protein 2 (IGFBP2). If the liver does not release enough IGFBP2 into the blood, the balance of the glucose and lipid metabolism may be disrupted. The research team led by Schürmann and Professor Matthias Schulze, head of the Department of Molecular Epidemiology at DIfE, therefore investigated how the diminished effect of the IGFBP2 gene could influence the development of type 2 diabetes.

Human studies show that people suffering from fatty liver produce and release less IGFBP2. Schürmann’s team observed similar effects in earlier mouse experiments, which showed that IGFBP2 levels were already reduced prior to the liver disease. This is due to the transfer of methyl groups at certain sites of the IGFBP2 DNA sequence, which inhibited the gene in the liver. These so-called epigenetic changes are caused, among other things, by lifestyle factors. Such modifications of the DNA in the IGFBP2 gene were also previously detected in blood cells of overweight people with impaired glucose tolerance.

Translational research from mouse to human studies

The interdisciplinary research team led by Schürmann and Schulze used findings from the clinic and laboratory to evaluate blood samples and data from the EPIC Potsdam Study. “This study is a good example of how translational research works: A clinical finding is taken up, analyzed mechanistically in the laboratory and finally examined in a population-wide study,” said Schürmann.

Recent analyses by the researchers indicate that inhibition of the IGFBP2 gene promotes type 2 diabetes. In addition, the team of scientists observed that leaner study participants and study participants with lower liver fat levels had higher concentrations of the protective binding protein in the blood. Higher plasma concentrations of IGFBP2 were associated with a lower risk of developing type 2 diabetes in subsequent years. “Our study confirms the hypothesis that the IGF-1 signaling pathway also plays an important role in the development of type 2 diabetes in humans,” added Dr. Clemens Wittenbecher, research associate in the Department of Molecular Epidemiology at DIfE and first author of the study.

Source: Read Full Article