Category: Metabolic Disorders

Categories : Ageing Metabolic DisordersTags :

Mouse Study Highlights Potential Therapeutic for Metabolic Syndrome

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Mopping up free radicals with antioxidants was a major health fad in the 1970s. In an effort to supposedly blunt the effects of aging and stave off chronic disease, people took huge amounts of antioxidants in the form of minerals and vitamins. Not only was this ineffective, it sometimes caused harm because untargeted antioxidants also compromised beneficial cellular signalling pathways. As theories of mitochondrial causes of disease fell out of favour, this health fad disappeared along with bell bottoms and disco.

Now, research recently published in Free Radical Biology and Medicine suggests a new way of dealing with free radicals: rather than mop them up, take a pill that selectively keeps them from being produced in the first place. Building on this work, collaborative research between the Buck and Calico Labs shows that specifically inhibiting free radical production at a particular mitochondrial site prevents and treats metabolic syndrome in mice, by preventing and reversing insulin resistance.

“We think that mitochondrial radical production drives many chronic diseases of aging, and that blocking the production of free radicals is a viable disease-treating and anti-aging intervention,” said Martin Brand, PhD, Buck Professor Emeritus and senior investigator of the study. “We’ve found a way to selectively keep problematic free radicals in check without compromising normal energy production in the mitochondria. These compounds act like a cork in a wine bottle. They plug a specific site so that it doesn’t produce free radicals, without hindering the mitochondria’s critical function of energy metabolism. We look forward to continuing this groundbreaking area of research.”

The orally bioavailable compound that has been developed, S1QEL1.719 (a new “S1QEL” – Suppressor of site IQ Electron Leak), was given both prophylactically and therapeutically to mice fed a high-fat diet that causes metabolic syndrome. Treatment decreased fat accumulation, strongly protected against decreased glucose tolerance and prevented or reversed the increase in fasting insulin levels by protecting against the development of insulin resistance.

Acting on mitochondrial complex I highlights potential interventions for other conditions

S1QEL1s act on site IQin mitochondrial complex I. (The mitochondrial electron transport chain consists of four protein complexes integrated into the inner mitochondrial membrane. Together they carry out a multi-step process, oxidative phosphorylation, through which cells derive 90% of their energy.)

First author and Buck staff scientist Mark Watson, Ph.D., says current literature strongly implicates complex I in a number of different diseases, from metabolic syndrome to Alzheimer’s, fatty liver disease, and noise-induced hearing loss, as well as the underlying aging process itself.

“S1QELs don’t sequester oxidants or radicals. Rather, they specifically inhibit radical production at the IQ site on complex I without interfering with other sites,” Watson said. “So the normal redox signaling that we require in our cells will continue. S1QELs just modulate that one site. They are very clean, very specific, and do not disrupt mitochondrial functioning like inhibitors of mitochondria do.”

Brand says the data shows that free radical production from complex I is an essential driver of insulin resistance and metabolic syndrome, a major disease of poor lifestyle choices and of aging. He says this feature is a strong reason to revisit the mitochondrial theory of aging. “These compounds fine-tune mitochondrial production of free radicals,” he said. “And it’s really interesting; just inhibiting this specific site improves the whole redox environment and prevents metabolic disease, and that is amazing.”

Source: Buck Institute for Research on Aging

Categories : Metabolic Disorders Neurodegenerative DiseasesTags :

Fluctuating Cholesterol and Triglyceride Levels Linked to Developing Dementia

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Older people who have fluctuating levels of total cholesterol and triglycerides may have a higher risk of Alzheimer’s disease and related dementias compared to people who have steady levels, according to new research published online in Neurology. Since the study is observational, it cannot establish a causative link.

“Prevention strategies for Alzheimer’s and related dementias are urgently needed,” said study author Suzette J. Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota. “Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care. Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia and ultimately determine whether levelling out these fluctuations could play a role in reducing dementia risk.”

Researchers used health care data to identify 11 571 people age 60 or older without a prior diagnosis of Alzheimer’s disease or dementia. They assessed total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) for the participants on at least three different days in the five years before the start of the study. Then participants were assigned into five equal groups based on the degree of measurement fluctuation, from lowest to highest.

Participants were followed for an average of 13 years. During that time, 2473 of them developed Alzheimer’s disease or another form of dementia. After adjusting for confounding variables, researchers found for total cholesterol, participants in the highest fluctuation group had a 19% increased risk of dementia compared to those in the lowest group. Of the 2311 people in the highest group, 515 developed dementia compared to 483 of the 2311 people in the lowest group. For triglycerides, those in highest group had a 23% increased risk.

No link was found between dementia and variations in LDL and HDL, however.

“It remains unclear why and how fluctuating levels of cholesterol and triglycerides are related to the risk of Alzheimer’s disease,” said Bielinski. “Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies.”

One study limitation was that researchers looked at Alzheimer’s disease and related dementias as a whole and did not differentiate between the types of dementia.

Source: American Academy of Neurology

Categories : Metabolic DisordersTags :

More Adolescents Are Underestimating Their Body Weight

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A study involving more than 745 000 adolescents from 41 countries across Europe and North America identified an increase in the amount of teenagers who underestimate their body weight. Tracking data from 2002 to 2018, the findings, published in Child and Adolescent Obesity, also show fewer adolescents overestimating their weight.

The team of international experts, who carried out the research, warn these shifting trends in body weight perception could reduce the effectiveness of public health interventions aimed at weight reduction in young people.

“During this impressionable age, body weight perception may influence a young person’s lifestyle choices, such as the amount and types of food they eat and their exercise habits,” says lead author Doctor Anouk Geraets, from the Department of Social Sciences, at the University of Luxembourg.

“So it’s concerning that we’re seeing a trend where fewer adolescents perceive themselves as being overweight — as this could undermine ongoing efforts to tackle increasing levels of obesity in this age group. Young people who underestimate their weight and therefore do not consider themselves to be overweight may not feel they need to lose excess weight and, as a result, they may make unhealthy lifestyle choices.”

A person’s perception of their body weight may not accurately reflect their actual weight. A discrepancy in body weight perception (BWP) may either be an underestimation (where actual weight is higher than perceived weight) or an overestimation (where actual weight is lower than perceived weight).

In the present study, the researchers examined survey data from 746,121 11-, 13- and 15-year-olds from 41 countries collected at four-yearly intervals between 2002 and 2018 in the International Health Behavior in School-Aged Children (HBSC), a WHO collaborative study.

The team modeled trends in BWP among adolescents across different countries over time, making adjustments for age, gender, and family socioeconomic status. They found:

  • Underestimation of weight status increased, and overestimation of weight status decreased over time among both sexes, with stronger trends for girls.
  • Correct weight perception increased over time among girls, while it decreased among boys.
  • Changes in correct weight perception, underestimation and overestimation of weight status differed across different countries — but these changes could not be explained by an increase in country-level overweight/obesity prevalence.

The authors speculated that the observed differences between girls and boys in BWP may support the idea there are sex differences in body ideals — and that these body ideals have changed over time. Notably, the increased underestimation and decreased overestimation of weight status over time for girls may be explained by the emergence of an athletic and strong body, as a new contemporary body ideal for both sexes.

“This study has clinical and public health implications. The increase in correct weight perception and the decrease in overestimation may have a positive effect on unnecessary and unhealthy weight loss behaviors among adolescents, while the increase in underestimation might indicate the need for interventions to strengthen correct weight perception,” says lead author Doctor Anouk Geraets.

“More research is now needed to understand the factors underlying these time trends and to develop effective public health interventions.”

While the large number of participating countries is a strength of the present study, but as these only included countries in Europe, the USA and Canada, the results can’t be generalised to other regions. In addition, although steps were taken to adjust the models for certain potential confounding factors, several other factors – such as body image, dieting, changing eating patterns, or migration – may also have played a role in the observed trends over time.

Source: Taylor & Francis Group

Categories : Exercise Metabolic DisordersTags :

For People with T2DM, Type and Timing of Physical Activity Matters

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An analysis on the positive effects of exercise on blood sugar levels in people with Type 2 diabetes mellitus (T2DM) shows that while all exercise helps, certain activities – and their timing – are especially beneficial. The study, published in The American Journal of Medicine, provides a comprehensive but straightforward summary of the benefits of exercise on controlling blood glucose levels in people with T2DM.

“The challenge with this is that most, if not all, people know exercise is good for them but they don’t know the best approach,” said Steven Malin, an associate professor in the Department of Kinesiology and Health at the Rutgers School of Arts and Sciences and an author of the study. “We targeted this issue by focusing on a few key parameters: the utility of aerobics versus weightlifting, the time of day that is optimal for exercise, whether to exercise before or after meals and whether we have to lose weight to get benefits or not.”

As part of the analysis, researchers sifted through dozens of studies and extracted common conclusions. Some of the key findings include:

  • Habitual aerobic exercise: increases the heart rate and the body’s use of oxygen helps manage blood glucose.
  • Resistance exercise: benefits insulin sensitivity in those with Type 2 diabetes.
  • Movement throughout the day by breaking up sitting time benefits blood glucose control and insulin levels.
  • Performing exercise later in the day can result in better control of blood sugar levels as well as improve insulin sensitivity.

“In short, any movement is good and more is generally better,” Malin said. “The combination of aerobic exercise and weightlifting is likely better than either alone. Exercise in the afternoon might work better than exercise in the morning for glucose control, and exercise after a meal may help slightly more than before a meal. And, you don’t have to lose weight to see the benefits of exercise. That is because exercise can lower body fat and increase muscle mass.”

While insulin resistance in T2DM is harmful, scientists believe increased insulin sensitivity is beneficial. High insulin sensitivity allows the cells of the body to use blood glucose more effectively, reducing blood sugar.

Malin researches insulin sensitivity and teaches kinesiology, the study of human movement. He and several other faculty members at Rutgers support the concept of “exercise as medicine.” The idea, which is supported by the American College of Sports Medicine and is increasingly being borne out by research, is that exercise can be considered a first-line therapy.

“I’m one of those individuals who subscribes to that notion, and in that way, I think of exercise as a drug,” Malin said.

Malin and colleagues authored the study to offer the medical community up-to-date practical advice for their patients.

“Together, this idea of exercise timing and type is important because it helps medical professionals more accurately recommend exercise prescriptions to combat high blood glucose,” Malin said.

Source: Rutgers University

Categories : Metabolic DisordersTags :

Even Modest Alcohol Intake Does not Reduce Diabetes, Obesity Risk

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Having only one or two alcoholic drinks per day does not protect against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Journal of Clinical Endocrinology & Metabolism.

It is widely accepted that excessive alcohol consumption causes a wide range of health issues and is thus a major public health concern. Whether modest alcohol consumption has beneficial health effects remains controversial, however, due to the limited power of observational studies.

The researchers used mendelian randomisation (MR), which can help to mitigate biases due to confounding and reverse causation in observational studies, and evaluate the potential causal role of alcohol consumption.

“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, PhD, from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc) as well as increased risk of type 2 diabetes.”

The researchers assessed self-reported alcohol intake data from 408 540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes. An extra drink per week was associated with an increased of 8% for diabetes risk and 10% for obesity risk.

These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.

Source: The Endocrine Society

Categories : Metabolic Disorders Substance UseTags :

Women’s Lean Body Mass and Age Speed up Blood Alcohol Elimination

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The rate at which women eliminate alcohol from their bloodstream is largely predicted by their lean body mass, although age plays a role, too, scientists found in a new study published in the journal Alcohol Clinical and Experimental Research. Since women with obesity also have more lean body mass, older women with obesity clear alcohol from their systems 52% faster than younger women of healthy weights, the study found.

“We believe the strong relationship we found between participants’ lean body mass and their alcohol elimination rate is due to the association that exists between lean body mass and lean liver tissue – the part of the liver responsible for metabolising alcohol,” said research group leader M. Yanina Pepino, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.

To explore links between body composition and alcohol elimination rates, the team conducted a secondary analysis of data from a study performed at and another at Indiana University, Indianapolis. Both projects used similar methods to estimate the rate at which alcohol is broken down in the body.

The combined sample from the studies used in the analysis included 143 women who ranged in age from 21 to 64 and represented a wide range of body mass indices – from healthy weights to severe obesity. Among these were 19 women who had undergone different types of bariatric surgery. Lean body mass is total body weight minus fat.

In a subsample of 102 of these women, the researchers had measured the proportions of lean and fat tissue in their bodies and calculated their body mass indices. Based on their BMI, those in the subsample were divided into three groups: normal weight (BMI of 18.5–24.9), overweight BMI (25–29.9) and obese (BMI 30+).

As the researchers expected, women with higher BMI had not only more fat mass than women of healthy weights, they also had more lean mass. On average, the group with obesity had 52.3 kg of lean mass, compared with 47.5 kg for the normal weight group.

The two studies both used an alcohol clamp technique, where participants received an intravenous infusion of alcohol at a rate controlled by a computer-assisted system. The system calculated personalised infusion rates based upon each participant’s age, height, weight and gender and was programmed so they would reach a target blood alcohol concentration of .06% within 15 minutes and maintain that level for about two hours

Using a breathalyser, breath samples were collected at regular intervals throughout the experiments to estimate participants’ blood alcohol concentration and provide feedback to the system.

“We found that having a higher fat-free body mass was associated with a faster alcohol elimination rate, particularly in women in the oldest subgroups,” said Neda Seyedsadjadi, a postdoctoral fellow at the university and the first author of the study.

“The average alcohol elimination rates were 6 grams per hour for the healthy weight group, 7 grams for the overweight group, and 9 grams for the group with obesity,” she said. “To put this in perspective, one standard drink is 14 grams of pure alcohol, which is found in 12 ounces of beer, 5 ounces of table wine or 1.5 ounces shot of distilled spirits.”

The interaction between participants’ age and lean body mass accounted for 72% of the variance in the time required to eliminate the alcohol from their system, the team found.

Pepino, who also holds an appointment as a health innovation professor at Carle Illinois College of Medicine, has conducted several studies on alcohol response in bariatric surgery patients.

The findings also shed light on alcohol metabolism and body composition in women who have undergone weight loss surgery. Researchers have long known that bariatric surgery alters women’s response to alcohol but were uncertain if it affected how quickly they cleared alcohol from their systems.

Some prior studies found that these patients metabolised alcohol more slowly after they had weight loss surgery. The new study’s findings indicate that these participants’ slower alcohol elimination rates can be explained by surgery-induced reductions in their lean body mass. Weight loss surgery itself had no independent effects on patients’ alcohol elimination rates, the team found.

Source: University of Illinois at Urbana-Champaign

Categories : Diet and Nutrition Metabolic DisordersTags :

Intermittent Fasting Might be a Good Idea for Preventing Diabetes

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New research from the University of Georgia suggests that the intermittent fasting fad might actually reduce the risk of diabetes. Published in Nutrients, the review found that time-restricted eating may reduce the chances of developing Type 2 diabetes and improve overall health.

Time-restricted eating involves having regular but fewer meals, cutting out late-night snacks and not eating for 12 to 14 hours (often overnight). After a comprehensive review of published, peer-reviewed studies, the researchers found a connection between number of meals and obesity and Type 2 diabetes.

“What we’ve been taught for many decades is that we should eat three meals a day plus snacking in between,” said Krzysztof Czaja, an associate professor of biomedical sciences in UGA’s College of Veterinary Medicine. “Unfortunately, this appears to be one of the causes of obesity.” The study was co-authored by Carlee Harris, an undergraduate biology major in UGA’s Franklin College of Arts and Sciences.

The three meals and snacks style of eating prevents insulin levels from going down during the day, and, with the amount of calories and sugars Americans consume on average, that can overload the body’s insulin receptors. That leads to insulin resistance and often Type 2 diabetes.

“That’s why it’s so hard to lose body fat,” Czaja said. “We are not giving our bodies a chance to use it. Having fewer meals a day will allow these fat deposits to be used as an energy source rather than the sugar we keep consuming.”

Modern eating approach disrupts body’s biological clock

The researchers found that time-restricted eating allows the body to relax and lower insulin and glucose levels, which in turn can improve insulin resistance, brain health and glycaemic control. It can also reduce calorie intake by around 550 calories per day without the stress of calorie counting.

Previous studies have shown disruptions to sleep and meal schedules can change both the type and amount of bacteria and other microorganisms in the digestive tract. But fasting may positively alter the gut microbiome, potentially staving off inflammation and a variety of metabolic disorders.

Additionally, the review suggests time-restricted eating can help regulate hormones responsible for appetite regulation and energy levels.

Regular meal schedules, eating breakfast and decreasing meals and snacks can help guard against obesity and Type 2 diabetes, according to the publication. And all breakfasts aren’t created equal. Aim for healthy fats and protein, like eggs, and avoid the sugar-filled breakfast cereals and pastries.

Although time-restricted eating appeared to improve health, the researchers found that other types of restricted eating, such as fasting for days on end, provided few benefits.

Regular but fewer meals can stave off obesity and metabolic disorders

The modern approach of three meals plus snacks became popular decades ago, and it’s a hard pattern to break.

“But our gut-brain signalling is not designed for this type of eating,” Czaja said.

The researchers caution that eating is not a one size fits all situation. Smaller, less active people need fewer calories on average than taller athletes, for example. So for some, one meal of nutrient-rich food might be another while others may need more.

But one thing was very clear from the literature they reviewed: Fewer meals of high-quality food is a good guideline for individuals at risk of developing Type 2 diabetes and obesity.

“Also definitely avoid late-night eating,” Czaja said. “Our midnight snacks spike insulin, so instead of us going into a resting state when we sleep, our GI is working on digestion. That’s why we wake up in the morning tired – because we don’t get enough resting sleep.”

Source: University of Georgia

Categories : Metabolic DisordersTags :

DNA Study Hints at How Insulin Resistance Develops after Glucose Challenge

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A study of the DNA of more than 55 000 people worldwide has shed light on what goes wrong in a glucose challenge that might lead to type 2 diabetes. The findings, published today in Nature Genetics, suggests that genetic changes relating to a protein called GLUT4 could be involved.

Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.

Most studies to date of insulin resistance have focused on the fasting state when insulin is largely acting on the liver.  But most people’s time is spent in the fed state, when insulin acts on muscle and fat tissues.

It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.” 

To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55 000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.

The team identified new 10 loci (genome regions) associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.

One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.

To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.

Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. The less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.

Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”

Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.

Source: University of Cambridge

Categories : Metabolic DisordersTags :

Safety and Efficacy of Oral Semaglutide Shown in Clinical Trial Success

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Participants taking a daily 50mg dose of oral semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, lost more weight than those taking placebo, according to results announced by the manufacturer, Norvo Nordisk.

Novo Nordisk announced headline results from phase 3a trial in a statement. The OASIS 1 trial is a 68-week, efficacy and safety trial comparing once-daily oral semaglutide 50mg for weight management to placebo in 667 adults with obesity or overweight with one or more comorbidities. Participants also undertook lifestyle interventions.

When evaluating the effects of treatment if all people adhered to treatment from a mean baseline body weight of 105.4 kg, people treated with oral semaglutide 50mg achieved a statistically significant weight loss of 17.4% after 68 weeks compared to a 1.8% reduction with placebo. In addition, 89.2% of those who received oral semaglutide 50mg, reached a weight loss of 5% or more after 68 weeks, compared to 24.5% with placebo.

When applying the treatment policy estimand, people treated with oral semaglutide 50 mg achieved a superior weight loss of 15.1% compared to a reduction of 2.4% with placebo and 84.9% achieved a weight loss of 5% or more, compared to 25.8% with placebo.

“We are very pleased with the weight loss demonstrated by the once-daily oral formulation of semaglutide in obesity. The results show comparable weight loss as in the STEP 1 trial with injectable semaglutide 2.4mg in obesity branded as Wegovy®”, said Martin Holst Lange, executive vice president for Development at Novo Nordisk. ”The choice between a daily tablet or weekly injection for obesity has the potential to offer patients and healthcare providers the opportunity to choose what best suits individual treatment preferences”.

Oral semaglutide 50 mg also appeared be safe and was well tolerated, with the most common adverse events being mostly mild to moderate gastrointestinal ones consistent with the GLP-1 receptor agonist class. Gastrointestinal adverse events were most prominent during dose escalation.

Novo Nordisk expects to file for regulatory approval in the US and the EU in 2023. The global launch of oral semaglutide 50mg is contingent on portfolio prioritisations and manufacturing capacity.

Source: Novo Nordisk

Categories : Metabolic Disorders PaediatricsTags :

Cholesterol may Explain The Link Between Childhood Obesity and Early Puberty

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As childhood obesity increases the world, children are entering puberty earlier and earlier – particularly girls. According to a survey, the onset of puberty occurs on average three months earlier for girls in every decade since 1977. Early, or precocious, puberty can leave children with psychological and social problems, as well leading to shorter adult heights. Studies also suggest that early puberty can increase the risk of developing cancer, diabetes, depression and cardiovascular disease later on in life.

While a scientific explanation has been lacking, the link between childhood obesity and early puberty has long been apparent. The more body fat a child has, the greater their likelihood of beginning puberty at an earlier age. Now, researchers have found what may be part of the answer in Drosphila fruit flies, publishing their results in Current Biology.

“Cholesterol is a fat. So, if you’re overweight, your body fat harbours more cholesterol. And it turns out that higher cholesterol is a key to earlier maturation in the fruit fly, our model organism. Our results demonstrate that the amount of cholesterol in adipose tissue and in certain support cells in the brain affects the growth of fruit flies and controls when they reach maturity,” explains Professor Kim Rewitz, a lead author of the study.

He adds, “And because the systems in fruit flies and humans are remarkably similar, we believe that the same may apply to humans – ie, that cholesterol in adipose tissue may help explain the connection between childhood obesity and early puberty.”

Puberty at ‘critical weight’

Professor Rewitz and the University of Copenhagen’s Department of Biology research team tested their hypothesis by putting fruit fly larvae on a “fatty diet” of cholesterol-packed foods. The development of these larvae was compared with larvae on a normal diet.

“We observed that larvae on the cholesterol diet consistently grew faster and entered ‘puberty’ sooner. It turned out that the increase of cholesterol stored in the fruit flies’ body fat and support cells in the brain increases the release of growth hormones that cause the animals to grow faster. Growth and size is a signal to the body for when to trigger puberty,” says Kim Rewitz. 

The professor explains that in fruit flies, the signal to undergo maturation is when their weight and amount of body fat reach a certain point during development:

“In one way or another, animals need to know when they’re large enough to reach sexual maturity and be able to reproduce. Organisms have a checkpoint in their development that they must pass to enter puberty known as ‘Critical Weight’. This checkpoint is found in fruit flies and most likely in humans too. This means that both fruit fly larvae and children probably need to reach a certain body size and have a certain amount of fat stored to enter puberty. What we’ve found is that the amount of cholesterol stored in body fat plays an important role in this process.

“We see that fruit flies have a mechanism that senses how much cholesterol is stored in their body fat and support cells in the brain. At a certain point, the system then sends a signal to the brain centres that triggers maturation by producing steroid hormones. In humans, these correspond to testosterone and oestrogen.”

However, it also means that if the amount of stored cholesterol increases, the organism can actually fail to estimate its overall size accurately, so that it hits the critical weight checkpoint earlier than it normally would:

“Because overweight children have more body fat, they will probably also have stored more cholesterol at an earlier point in their development. So, if our assumption that the same mechanism exists in humans holds true, it could help to explain early puberty in obese children,” says the researcher.

Cholesterol may influence cancer as well

Professor Rewitz concludes that with part of the puzzle in hand, scientists can search for more clues and treatment. In the meantime, lifestyle changes remain the best solution for childhood obesity.

Professor Rewitz and his research colleagues have now started to look deeper into the significance of the cholesterol mechanism for cancer development. Their research also shows that, via the same mechanism, cholesterol can activate cell growth that leads to cancer.

Source: University of Copenhagen