Tag: obesity

A New Bacterium Might Help Treat Type 2 Diabetes and Obesity

E. Coli bacteria. Image by CDC
E. Coli bacteria. Image by CDC

A newly discovered bacterium has been shown to have a possible link to type 2 diabetes and obesity, and may yield pathways to possible treatments.

It began when Patrice Cani, FNRS researcher at University of Louvain (UCLouvain), and his team repeatedly observed that a certain bacterium, Subdoligranulum, is usually lacking in obese and diabetic people, while it is systematically present in healthy people. Based on this, they decided to examine this family of bacteria.

Currently only one cultivated strain of this family is available in the world (the only known member of a large family) and was not the strain that was seen to be decreased in obese and diabetic people. This is not unusual: nearly 70% of bacteria in the intestine have not yet been identified — this is called the dark matter of the intestine.

In 2015, the team then set out to isolate the bacterium themselves in order to learn about its action on the human body, knowing that it is only present in healthy people. To find a second member of the family, the scientists spent two years searching, isolating and cultivating nearly 600 intestinal bacteria. 

All of this was in vain. Instead, the UCLouvain team uncovered a bacterium of a new, previously unknown kind. They named it Dysosmobacter welbionis: Dysosmo (“which smells bad”, in Greek), bacter (bacterium) is the bacterium which stinks, “Because, when you grow it, it has a slight odour,” they explained. Welbionis for WELBIO, the organisation in the Walloon region which funded this research.

The bacterium is peculiar for a number of reasons, including the fact that it produces butyrate. Though many other bacteria produce this colon cancer-promoting molecule, for example by strengthening the intestinal barrier and boost immunity. But the team also discovered that Dysosmobacter welbionis was less present in people with type 2 diabetes.

By analysing the microbiota from 12 000 faecal samples gathered from around the world, the UCLouvain scientists observed that the bacteria is present in 70% of the population. As to why such a widely prevalent bacteria was never discovered before, the answer likely lies in the improved cultivation techniques developed by the UCLouvain team.

The UCLouvain team including doctoral student Emilie Moens de Hase and post-doctoral fellow Tiphaine Le Roy then tested the action of Dysosmobacter welbionis in mice. The Results? The bacteria increased the number of mitochondria (a kind of power plants within cells that burns fat), thereby lowering sugar levels and weight, in addition to having strong anti-inflammatory effects. All these effects are very promising for type 2 diabetic and obese subjects and resemble those of Akkermansia, a beneficial bacterium that is at the heart of the research in Patrice Cani’s lab.

They also observed that the bacteria’s effects are not limited to the gut: Scientists have found that certain molecules produced by Dysosmobacter migrate around the body and have distant actions as well. This could explain the effects the bacteria have on the fat tissues, and also opens the doors for a possible impact on other diseases such as cancer. This is currently being investigated by the team.

The next step is to test the action of Dysosmobacter welbionis coupled with that of Akkermansia, in order to see if their association has cumulative effect on health, while always keeping in mind the fight against type 2 diabetes, inflammatory diseases, obesity and cancer. “That’s the fun of research: you dig for dinosaur bones and you end up finding a treasure,” Patrice Cani enthused.

Source: Université catholique de Louvain

Journal reference: Roy, T. L., et al. (2021) Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut. doi.org/10.1136/GUTJNL-2020-323778.

‘Game-changing’ Weight Loss Drug Semaglutide Approved by FDA

Image source: Neonbrand on Unsplash

The US Food and Drug Administration approved a ‘game changing’ weight loss drug called Wegovy (semaglutide) for chronic weight management in adults with obesity or overweight.

This injection is the first drug for chronic weight management in adults with general obesity or overweight to be approved since 2014. The drug is indicated for chronic weight management in patients with a body mass index (BMI) of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater, and is to be used in conjunction with diet and exercise.

“Today’s approval offers adults with obesity or overweight a beneficial new treatment option to incorporate into a weight management program,” said John Sharretts, MD, deputy director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “FDA remains committed to facilitating the development and approval of additional safe and effective therapies for adults with obesity or overweight.”

Approximately 70% of American adults have obesity or overweight, and >67% of sub-Saharan Africans. This is a serious health issue linked to leading causes of death such as heart disease, stroke and diabetes, and also to increased risk of certain types of cancer. Losing 5% to 10% of body weight through diet and exercise has been associated with a reduced risk of cardiovascular disease in adult patients with obesity or overweight.

Wegovy works by mimicking a hormone called glucagon-like peptide-1 (GLP-1) that targets areas of the brain regulating appetite and food intake. The medication dose must be increased gradually over 16 to 20 weeks to 2.4 mg once per week to reduce gastrointestinal side effects.

The drug’s safety and efficacy were studied in four 68-week trials. Over 2600 patients received Wegovy for up to 68 weeks in these four studies and more than 1500 patients received placebo.

The largest placebo-controlled trial enrolled diabetes free adults with an average age of 46 years, and 74% of whom were female. The average body weight was 105 kg and average BMI was 38 kg/m2. Individuals receiving Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes. The average age was 55 years and 51% were female, with an average body weight of 100 kg and average BMI of 36 kg/m2. In this trial, individuals receiving Wegovy lost 6.2% of their initial body weight compared to the placebo group.

“The approval of Wegovy in the US brings great promise to people with obesity. Despite the best efforts to lose weight, many people with obesity struggle to achieve and maintain weight loss due to physiological responses that favour weight regain,” said Martin Holst Lange, executive vice president, Development at Novo Nordisk. “The unprecedented weight loss for an anti-obesity medication marks a new era in the treatment of obesity, and we now look forward to making Wegovy available to people living with obesity in the US”.

Unfortunately, the drug may be out of the reach of many people in need of it, with indications being that the medication may be charged at around US$1,300 a month.

Source: Food and Drug Administration

Milk Consumption Does Not Raise Cholesterol Levels

Photo by ROBIN WORRALL on Unsplash

Regular consumption of milk is not associated with increased levels of cholesterol, according to new research.

A study published in the International Journal of Obesity analysed three large population studies and found that people who regularly drank high amounts of milk had lower levels of both ‘good’ and ‘bad’ cholesterol, although their BMI levels were higher than non-milk drinkers. Analysis of other large studies also suggests that regular milk drinkers had a 14% lower risk of coronary heart disease.

The team of researchers took a genetic approach to milk consumption by looking at a variation in the lactase gene associated with digestion of lactose. The study found that this gene variation for digesting lactose was a good identifier for people who consumed higher levels of milk.

“We found that among participants with a genetic variation that we associated with higher milk intake, they had higher BMI, body fat, but importantly had lower levels of good and bad cholesterol,” said Vimal Karani, Professor of Nutrigenetics and Nutrigenomics at the University of Reading said. “We also found that those with the genetic variation had a significantly lower risk of coronary heart disease. All of this suggests that reducing the intake of milk might not be necessary for preventing cardiovascular diseases.”

Contradictory research on the effect of high dairy intake and obesity and metabolic disorders was the motivation for the study. To exclude the effects of differences in sampling size, ethnicity and other factors, the team conducted a meta-analysis of data in up to 1.9 million people, including the UK Biobank and used the genetic approach to avoid confounding.

Even though the UK Biobank data showed that those with the lactase gene had an 11% reduced risk of type 2 diabetes, the study did not find a link between higher milk intake and increased likelihood of diabetes or related traits, such as glucose and inflammatory biomarkers.

“The study certainly shows that milk consumption is not a significant issue for cardiovascular disease risk even though there was a small rise in BMI and body fat among milk drinkers. What we do note in the study is that it remains unclear whether it is the fat content in dairy products that is contributing to the lower cholesterol levels or it is due to an unknown ‘milk factor’,” said Professor Karani.

Source: EurekaAlert

Journal information: Karani Santhanakrishnan Vimaleswaran et al, Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals, International Journal of Obesity (2021). DOI: 10.1038/s41366-021-00841-2

Rise in Obesity Impeding Cancer Fight

Though cancer death rates have fallen dramatically in the United States, those from obesity-related cancers are falling much more slowly.

In a study published this week in JAMA Network Open, researchers found that obesity-related cancer deaths are improving, but at a slowing pace.

Researchers at the University of North Carolina Gillings School of Global Public Health drew on mortality data for 50 million people, cancer deaths not associated with obesity — such as lung or skin cancer – are declining at a rate almost three times faster than obesity-related cancers, such as stomach, colorectal, uterine, thyroid and postmenopausal breast cancer.

“These are cancers where we could see even larger mortality improvements with creative and practical tools to combat obesity,” said study senior author Hazel B Nichols, PhD, associate professor in the Department of Epidemiology at the UNC Gillings School.

Most Americans are over the recommended body weight, and being overweight or obese puts them at risk for certain cancers.  

Extra body fat can lead to changes in the body that can contribute to cancer development, such as long-lasting inflammation and higher than normal levels of insulin and hormones that can fuel cell growth, according to the U.S. Centers for Disease Control and Prevention.

Discordant progress

Researchers use cancer death rates to track progress against cancer over time. The study authors set out to find out if obesity was stalling progress against cancer the way it did against heart disease. After 2011, heart disease mortality rates slowed their decline, a phenomenon which may be due to obesity.

“What was puzzling was that we didn’t see the same pattern of slower improvements when looking at cancer overall, which is surprising because obesity contributes to both cancer risk and heart disease risk,” said Dr Nichols. “When we focused on the differences between obesity-related cancers and non-obesity related cancers, we saw that improvements for obesity cancers were not as impressive — consistent with the pattern for heart disease.”

For example, the study showed that in 2011, 110 people out of 100 000 died from cancers not related to obesity. In 2018, the mortality rate for those cancers fell to 93.8 deaths per 100 00 people — a 2.29% annual decline.

During the same period, the decline for obesity-related cancers was much slower, changing from 58.4 to 54.9 deaths per 100 000 people, a rate of .83% — a rate one-third the decrease in non-obesity related cancers.

Obesity may also be contributing to more of the cancer deaths in the US. The study found that cancers not associated with obesity accounted for 66.8% of cancer deaths in 1999, decreasing to 62.6% in 2018.
The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation. Christy Leigh Avery, PhD

Falls in cancer deaths are the result of fewer smokers, along with better screening and treatments, according to the American Cancer Society.

But the findings by UNC researchers reinforce the impact of obesity on cancer. 

“Obesity is a risk factor for many, but not all, types of cancer,” Nichols Dr said. “We need to make maintaining a healthy weight an obtainable goal for everyone in terms of safe public spaces, the availability and affordability of nutritious foods, and other structural factors. The good news is that if we’re able to make these changes as a society, we will be able to improve the health of a nation.”

Source: University of North Carolina

Journal information: Avery CL, Howard AG, Nichols HB. Comparison of 20-Year Obesity-Associated Cancer Mortality Trends With Heart Disease Mortality Trends in the US. JAMA Netw Open. 2021;4(5):e218356. doi:10.1001/jamanetworkopen.2021.8356

Study Reveals More Secrets of Leptin’s Role in Appetite Control

A new study describes how leptin, an appetite-suppressing hormone released from adipose tissue, is involved in appetite suppression through the dopamine pathway.  

Since the discovery of leptin in the 1990s, many questions still remain over how it suppresses appetite. Now, a new study in mice describes novel neurocircuitry between midbrain structures that control feeding behaviours under the modulatory control of leptin.

Leptin links the body and the brain, providing information about its metabolic state and influencing energy balance. Animals deficient for leptin rapidly become obese without its regulatory control of feeding behaviour, showing just how important it is.

“This process is shaped by communication between bodily fat storages (via a hormone called leptin) and the brain’s dopamine reward system. This leptin-dopamine axis is critically important for body weight control, but its modes of action were not well understood,” said Roger Adan, PhD, Department of Translational Neuroscience, University Medical Centre Utrecht.

Not only does leptin suppress eating through signals to brain regions controlling eating behaviours, but it also lowers food’s reward value in the brain’s dopamine (DA) reward system. That food-reward pathway was known to involve dopaminergic neurons of the ventral tegmental area (VTA) signaling to the nucleus accumbens (NAc). However, these DA neurons do not have receptors for leptin.

The researchers mapped the new microcircuitry with a combination of technologies, including optogenetics, chemogenetics and electrophysiology.

“Although leptin receptors are present on [some] dopamine neurons that signal food reward, we discovered that leptin receptors are also present on inhibitory neurons that more strongly regulate the activity of dopamine neurons. Some of these inhibitory neurons suppressed food seeking when [animals were] hungry, whereas others [did so] only when [animals were] in a sated state,” said Professor Adan, also of the Department of Translational Neuroscience, University Medical Center Utrecht and University Utrecht.

John Krystal, MD, Editor of Biological Psychiatry, said of the study, “It turns out that leptin plays key modulatory roles in an elegant circuit that unites midbrain and limbic reward circuitry. By inhibiting hypothalamic neurons and ultimately suppressing the activity of dopamine neurons in the midbrain that signal reward and promote feeding, leptin reduces food intake in animals under conditions when caloric intake has exceeded energy use.”

Professor Adan concluded that, “Targeting these neurons may provide a new avenue for the treatment of anorexia nervosa and to support dieting in people with obesity.”

Source: News-Medical.Net

Journal information: Omrani, A., et al. (2021) Identification of novel neurocircuitry through which leptin targets multiple inputs to the dopamine system to reduce food reward seeking. Biological Psychiatry. doi.org/10.1016/j.biopsych.2021.02.017.

‘Obesity Paradox’ in Kidney Cancer Continues to Mystify

Obese patients with metastatic renal cell carcinoma (RCC) were more likely to survive compared to their normal weight counterparts when receiving immune checkpoint inhibitors (ICI), a study has shown.

RCC is the most deadly of the urogenital cancers, and its incidence is increasing. Males are twice as likely as females to develop it.
A team of researchers including Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, conducted an analysis of 735 metastatic RCC patients who received PD-1/L1 immunotherapies. 

Those with a BMI of 25 or greater had significantly longer overall survival (OS), with 1-year rates of 79% versus 66% for those with a BMI below that cutoff. This relationship was observed across tumour categories.

“These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era,” the team noted.

“Several hypotheses have attempted to explain this clinical observation in RCC,” Choueiri’s team wrote. “Low fatty acid synthase gene expression, which is inversely correlated with BMI, was associated with longer OS in VEGF-treated patients. Transcriptomic analysis suggests that patients with obesity have tumors with increased angiogenesis gene signatures and peritumoral adipose tissues with increased hypoxia, inflammation, and immune cell infiltration signatures.”

In 319 patients with next-generation sequencing technology, there was no difference between groups for tumour mutation burden, at an average 6.8 mutations per megabase for the low and high BMI groups. Genomic alteration frequency analysis also picked up no differences.

Limitations of the study authors included its retrospective nature, incomplete gene-expression profiling, and between-group imbalances. Patients with higher BMI had greater odds of having better performance status and being in more favourable risk groups, had greater odds of having clear cell histology, having had prior nephrectomy, and having received a checkpoint inhibitor as first-line therapy.

Source: MedPage Today

Journal information: AKA Lalani, et al “Assessment of immune checkpoint inhibitors and genomic alterations by body mass index in advanced renal cell carcinoma” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0019.

Regular Sleep Patterns in Toddlers Important for BMI

Although getting regular sleep patterns in toddlers has long been a priority for parents, researchers have shown it is important for toddlers’ BMI.

The researchers, led by Lauren Covington, an assistant professor in the University of Delaware School of Nursing, investigated the link between poverty, regular sleep patterns and BMI in toddlers. According to The National Sleep Foundation, toddlers 1- to 3-years-old should have 12 to 14 hours of sleep in a 24-hour period.

“We’ve known for a while that physical activity and diet quality are very strong predictors of weight and BMI,” said Prof Covington, the lead author of the article. “I think it’s really highlighting that sleep may be playing a bigger role here than it’s been given credit for.”

The researchers aimed to investigate the relationship between poverty and BMI in toddlers, and wanted to see whether sleep behaviour, activity or food intake could provide the explanation.

Using data from families in an obesity prevention trial, 70% of whom were below the poverty line, and all eligible for nutritional supplementation grants, Toddlers were given accelerometers to wear to measure physical activity and parents filled out food diaries.

The researchers found that children from households with greater poverty were more likely to have greater inconsistent bedtimes, and those with more inconsistent bedtimes had higher BMI percentages.

Prof Covington said this is likely to be a bidirectional relationship. “There’s a lot of teasing out the relationships of the mechanisms that are at play here, which is really difficult to do because I think they’re all influencing each other,” she said.

Having consistent bedtimes where children go to bed within one hour of the normal time is a recommended guideline, but for families in poverty this may be impossible for a variety of reasons. Single parent households and juggling multiple jobs are part of the challenges they face.

“Implementing a consistent bedtime could be one behavioural change that a family could potentially do,” said Prof Covington. “It’s more attainable than maybe getting healthy food at the grocery store or playing outside on the playground, especially now with the cold weather. Just having a consistent bedtime can help provide some sense of structure, but then maybe have better implications for health and BMI as well.”

Source: Medical Xpress

Journal information: Lauren Covington et al. Longitudinal Associations Among Diet Quality, Physical Activity and Sleep Onset Consistency With Body Mass Index z-Score Among Toddlers in Low-income Families, Annals of Behavioral Medicine (2020). DOI: 10.1093/abm/kaaa100

Why Antipsychotic Drugs Cause Weight Gain

A University of Pittsburgh study has discovered that the reason antipsychotic medications have weight gain as side effects is because the pancreas also produces and responds to dopamine.

Dopamine is a neurotransmitter involved in mood regulation, pleasure and reward signalling. Many psychological disorders are thought to involve dopamine imbalances and are treated by medications designed to this end.
“There are dopamine theories of schizophrenia, drug addiction, depression and neurodegenerative disorders, and we are presenting a dopamine theory of metabolism,” said lead author Despoina Aslanoglou, PhD, at the University of Pittsburgh. “We’re seeing now that it is not only interesting to study dopamine in the brain, but it is equally interesting and important to study it in the periphery.”

Senior author Zachary Freyberg, MD, PhD, assistant professor of psychiatry and cell biology at Pitt, observed that the dopamine theory is not as simple or as well understood as we would like to think.

“We still don’t really understand how dopamine signals biologically,” said Dr Freyberg. “Even decades after dopamine receptors have been discovered and cloned, we still deploy this ‘magical thinking’ approach: something happens that’s good enough. We use drugs that work on dopamine receptors, but how they intersect with this ‘magical system’ is even less understood.”

The researchers found that dopamine is not only produced in the brain but also in the alpha and beta cells of the pancreas, which secrete glucagon and insulin, respectively.

Alpha cells can produce their own dopamine with no precursors in response to glucose levels, while beta cells require an L-DOPA precursor. It may be possible that alpha cells secrete dopamine for their own receptors, while also supplying it to beta cells to suppress the release of insulin.

Surprisingly, the researchers also discovered that pancreatic dopamine can affect other receptors, such as noradrenaline and adrenaline.
At low concentrations, dopamine binds to D2-like dopamine receptors, blocking the release of glucagon or insulin. At high concentrations, dopamine binds to beta-adrenergic receptors, becoming stimulatory and pushing up glucagon levels while inhibiting insulin levels by blocking alpha-adrenergic receptors.

The study revealed how blocking inhibitory dopamine receptors causes an unchecked release of insulin and glucagon, leading to metabolic disorders and eventually, obesity and diabetes. This finding will help to formulate better drugs that target the dopamine system, reducing the effect on the pancreas.

Source: News-Medical.Net

Appetite Control With Semaglutide is a ‘Game Changer’ for Obesity

Semaglutide, a drug normally used to treat type 2 diabetes promises to make a huge impact in the fight against obesity and the diseases associated with it.

A 15 month study involving over 2000 participants resulted in an average weight loss of 15kg for those taking the appetite suppressing drug.   
Speaking to the BBC, Jan, one of the participants in the trial, lost 28kg, which was over a fifth of her body weight. “The drug changed my life and completely altered my approach to food,” she said.

She said dieting had made her “miserable” but taking the drug was completely different as she was less hungry. 

However, that the trial has ended for Jan, her appetite has returned to normal and she is gaining weight. She said: “It felt effortless losing weight while on the trial, but now it has gone back to feeling like a constant battle with food.”

Recently approved by the FDA and European Medicines Agency, semaglutide is normally used to treat type 2 diabetes as an adjunct to diet and exercise, but the trial sought to establish its use in higher doses as an appetite suppressant. One group was given a weekly semaglutide injection while the other received a placebo, and dietary and lifestyle guidance was given to both groups with the aim of losing weight. 
The drug mimics GLP-1, a hormone that is released after a meal. The trial participants receiving semaglutide lost an average of 15kg compared to 2.6kg for  placebo, with 32% of participants receiving semaglutide losing a fifth of their body weight compared to 2% for placebo.

Side effects included nausea, diarrhoea, vomiting and constipation.
Prof Sir Stephen O’Rahilly, from the University of Cambridge, said: “The amount of weight loss achieved is greater than that seen with any licensed anti-obesity drug.

“This is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side-effects.”

Dr Duane Mellor, a dietician and from Aston Medical School, said: “It is useful to have a potential option to help people lose weight, however we need to acknowledge that weight loss will still need lifestyle change, and that any medication or change in lifestyle can bring potential risks and side-effects.

“So, it is always wise to speak to a health professional before trying to lose weight.”

Source: BBC News

Eating Saturated Fats can Cut Symptoms of Pancreatitis

A study has found that symptoms of pancreatitis are less severe when foods with saturated fats are eaten.

The study, by researchers from Mayo Clinic, the Saint Louis University School of Medicine and the Washington University School of Medicine, examines the obesity paradox in which obese patients had better results when being treated for certain conditions, compared to non-obese patients.

Pancreatitis is the leading cause of hospitalisation from gastrointestinal disorders in the United States. It can have a variety of causes, such as gallstones, having abdominal surgery or overconsumption of alcohol.
Saturated fats are found in meat and dairy, while unsaturated fats are found in plants and fish, and in general consumption of unsaturated fats over saturated fats is encouraged as it is associated with reduced risk of heart disease and other conditions. However, exceptions such as the obesity paradox exist.

To delve into this question, the researchers examined 20 clinical reports from 11 countries, where fat intake in obese patients was monitored. They found that among obese patients who developed pancreatitis, those who ate a diet heavy in saturated fats had less severe symptoms than those who did not. 

To determine the cause of this protective effect, the researchers fed mice a diet rich in either saturated or unsaturated fats, and then induced pancreatitis in them. Those fed saturated fats developed less severe symptoms. On closer examination, they found that saturated fat did not interact well with pancreatic triglyceride lipase, reducing production of long-chain non-esterified fatty acids, which reduced the symptoms of pancreatitis.  

Source: Medical Xpress

Journal information: Biswajit Khatua et al. Adipose saturation reduces lipotoxic systemic inflammation and explains the obesity paradox, Science Advances (2021). DOI: 10.1126/sciadv.abd6449