Obesity research, news and discussion thread

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Researchers develop the first-ever ingestible electroceutical device to control appetite by hormone modulation
https://medicalxpress.com/news/2023-04- ... etite.html
by New York University

A team of researchers at NYU Abu Dhabi (NYUAD), led by Khalil Ramadi, assistant professor of bioengineering at NYU Tandon and the Director of the Laboratory for Advanced Neuroengineering and Translational Medicine at NYU Abu Dhabi, has developed a first-of-its-kind ingestible electroceutical device for the neuromodulation of the gut-brain axis, the signaling pathway between the gastrointestinal tract and central nervous system.

The ingestible capsule is a noninvasive and precise method that could be used to modulate hunger levels and treat metabolic and neurologic diseases. This was developed in collaboration with Professor Giovanni Traverso of MIT, who is a joint senior author of the study and James McRae, a graduate student at MIT, who is first co-author of the paper published in the journal Science Robotics.

The FLASH system uses electrodes on its surface to deliver electrical stimulation to stomach mucosal tissue. The gut-brain axis regulates several physiological functions, including feeding and emotional behavior. The existing pharmaceutical and surgical methods to modulate the axis, including implanting electrodes through surgery, are imprecise, invasive, and have been associated with significant recovery periods and associated risks.

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Powerful new obesity drug poised to upend weight loss care
Source: AP

By JONEL ALECCIA 58 minutes ago

As a growing number of overweight Americans clamor for Ozempic and Wegovy — drugs touted by celebrities and on TikTok to pare pounds — an even more powerful obesity medicine is poised to upend treatment.

Tirzepatide, an Eli Lilly and Co. drug approved to treat type 2 diabetes under the brand name Mounjaro, helped people with the disease who were overweight or had obesity lose up to 16% of their body weight, or more than 34 pounds, over nearly 17 months, the company said on Thursday.

The late-stage study of the drug for weight loss adds to earlier evidence that similar participants without diabetes lost up to 22% of their body weight over that period with weekly injections of the drug. For a typical patient on the highest dose, that meant shedding more than 50 pounds.

Having diabetes makes it notoriously difficult to lose weight, said Dr. Nadia Ahmad, Lilly’s medical director of obesity clinical development, which means the recent results are especially significant. “We have not seen this degree of weight reduction,” she said.

Read more: https://apnews.com/article/mounjaro-weg ... d40636752a

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New weapon found in fight to combat obesity, diabetes
By Bronwyn Thompson
May 31, 2023

An international team of scientists is one step closer to unlocking the molecular mechanisms at work in fat tissue, which could ultimately lead to treatments to effortlessly ‘switch on’ calorie burning.

For the first time, researchers at the University of East Anglia (UEA), the University of Cambridge, the University of Pennsylvania and the Free University of Brussels have viewed the molecular structure of mitochondrial uncoupling protein 1 (UCP1) in such detail that they have new insights into how it switches on to kickstart fat burning.

In brown fat (aka ‘good fat’) cells, UPC1 enables the tissue to burn calories as heat, which is vital in mammals for protection against the cold and to maintain body temperature. Brown fat is generally considered ‘good’, because of its key metabolic function, as opposed to white fat, which our bodies store calories in and is responsible for most negative health conditions linked to excess weight.

https://newatlas.com/science/protein-go ... -diabetes/

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Daily pill from Eli Lilly leads to 15% weight loss in midstage study, rivaling Wegovy results without the shot
Meg Tirrell
By Meg Tirrell, CNN

Eli Lilly’s experimental pill for weight loss helped people lose an average of 15% of their body weight after 36 weeks on the highest dose in a midstage trial, rivaling what’s seen with currently approved injectable therapies like Wegovy over longer durations.

The drug, orforglipron, had similar side effects as others in the class, known as GLP-1 receptor agonists: primarily gastrointestinal events like nausea, constipation and vomiting, researchers reported in a study published Friday in the New England Journal of Medicine. Results from the Lilly-funded trial were also presented at the American Diabetes Association conference in San Diego.

https://edition.cnn.com/2023/06/23/heal ... index.html

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Plant-based Food Packages Linked to Reduced BMI in Children
June 22, 2023

Introduction:

(Mass General Bringham via Eurekalert) A new study led by researchers from the Mass General Brigham healthcare system suggests that taking a “food is medicine” approach could increase nutrition security for families and lead to reductions in body mass index (BMI) in children. Working together with the MGH Food Pantry, researchers from the Massachusetts General for Children and Boston Children’s Hospital examined whether providing weekly plant-based foods to families seeking food assistance during the pandemic led to weight changes among children.

The team found an association between increasing receipt of food packages and decreased BMI. The findings, published in the journal Preventing Chronic Disease, add to a growing body of evidence that providing plant-based foods could be a useful strategy to prevent childhood obesity in children from food-insecure families.

“It’s important to encourage healthy eating habits during childhood to help prevent co-morbidities associated with obesity later in life, but many families to do not have access to expensive healthy foods, such as produce,” said senior author Lauren Fiechtner, MD, MPH, Director of the Pediatric Nutrition Center at Mass General for Children and Health and Research Advisor at The Greater Boston Food Bank. “Food pantries like MGH Revere that can provide families with healthy foods are a huge help in making sure that kids have a long, healthy future and have the best cardiovascular and metabolic health possible from a young age.”

Food insecurity increased by 55% percent in the United States in 2020, affecting 42% of households with children. This increase was driven by a variety of factors, such as the economic impacts of the pandemic, the closure of schools, and disruption of food supply chains. As food insecurity increased, so did the prevalence of childhood obesity, rising from 19.3% to 22.4% between August 2019 and August 2020.

For families dealing with food insecurity, the challenge is usually one of food quality as much as food quantity.

Read more here: https://www.eurekalert.org/news-releases/993006

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[wjfox]

New drug provides weight loss of 24%

30th June 2023

In a significant advance for the treatment of obesity, biotech giant Eli Lilly has announced the results from a trial of retatrutide, which produced a staggering 24.2% weight loss in patients.

[...]

A study published last year, in which people took the diabetes drug tirzepatide (sold under the brand name Mounjaro), found that a majority of those on the highest dose had a reduction in body weight of 20% or more after 72 weeks. The FDA approved Mounjaro for diabetes in May 2022 and is expected to approve it for weight loss in November 2023.

Now, an even greater percentage weight loss has been achieved, with a drug called retatrutide. Eli Lilly and Company has just published the results from a recent trial in The New England Journal of Medicine. The company also presented its findings at the recent American Diabetes Association conference held in San Diego.

The Phase 2 trial of retatrutide involved 338 adults, 52% of whom were men, each with a minimum BMI of 27. Participants on the highest dose achieved a mean weight reduction of 24.2%, translating to an average absolute weight reduction of about 58 lbs (26.3 kg) over 11 months of the study. Given that participants had not yet reached a weight plateau at the time the study ended, full efficacy could have been even higher if allowed to continue for longer.

[...]

"Obesity is a treatable chronic disease with a complex underlying biology. We are now in the midst of a rapidly expanding therapeutic landscape of potential highly effective treatment options for individuals with obesity," said Ania Jastreboff, PhD, study co-author and Director of the Yale Obesity Research Center.

https://www.futuretimeline.net/blog/202 ... meline.htm

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^^^I think the simple answer to obesity is a combination of a better diet and more exercise. Complicating that is that many people find it very difficult to find the time to do the needed amount of exercise. There is also a reluctance to adapt the kind of diet needed to address the problem. That also involves time in research, especially if there are other complicating medical issues. As a consequence, many are looking for a pill popping approach, something the pharmaceutical industry sees as an avenue for potential profit. I distrust the pill popping approach but can understand its attraction.

I have personally been rated as overweight but not obese for some time now. I switched to a plant-based diet and tried to cut back on processed foods. I also increased my level of exercise. I have thus lost weight although still technically within the overweight classification. Unfortunately, a recent blood test showed me with having higher triglyceride and low-density lipoprotein levels. So, its back to the drawing board for me.

The good news is that my high-density lipoprotein level is up.

Edit: I met with my physician. He indicated that although my triglyceride and low-density lipoprotein levels were high, they were not sufficiently elevated to be of great concern. He was also pleased with the description of my diet.

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Fiber is Your Body’s Natural Guide to Weight Management – Rather than Cutting Carbs Out of Your Diet, Eat Them in Their Original Fiber Packaging Instead
by Christopher Damman, M.D.
July 3, 2023

Introduction:

(The Conversation) Fiber might just be the key to healthy weight management – and nature packages it in perfectly balanced ratios with carbs when you eat them as whole foods. Think unprocessed fruits, vegetables, whole grains, beans, nuts and seeds. Research suggests that carbohydrates are meant to come packaged in nature-balanced ratios of total carbohydrates to fiber. In fact, certain types of fiber affect how completely your body absorbs carbohydrates and tells your cells how to process them once they are absorbed.

Fiber slows the absorption of sugar in your gut. It also orchestrates the fundamental biology that recent blockbuster weight loss drugs like Wegovy and Ozempic tap into, but in a natural way. Your microbiome transforms fiber into signals that stimulate the gut hormones that are the natural forms of these drugs. These in turn regulate how rapidly your stomach empties, how tightly your blood sugar levels are controlled and even how hungry you feel.

It’s as if unprocessed carbohydrates naturally come wrapped and packaged with their own instruction manual for your body on how to digest them.
I am a physician scientist and gastroenterologist who has spent over 20 years studying how food affects the gut microbiome and metabolism. The research is clear – fiber is important not just for happy bowel movements, but also for your blood sugar, weight and overall health.

Carbohydrates without their wrappers

Unfortunately, most Americans get the majority of their carbohydrates stripped of their natural fibers. Modern processed grains like white rice and white flour as well as many ultraprocessed foods like some sugary breakfast cereals, packaged snacks and juices have removed these fibers. They essentially come unwrapped and without instructions for the body on how much it should absorb and how it should process them. In fact, only 5% of Americans eat the recommended amount of carbohydrates with enough of their natural packaging intact. Guidelines recommend at least 25 to 30 grams of fiber a day from food.

Read more here: https://theconversation.com/fiber-is-y ... d-205159

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Scientists Find Hormone Pathway That May Speed Up Calorie Burning
by David Nield
July 4, 2023

Introduction:

(Science Alert) Losing weight isn't easy for most of us, and neither is keeping it lost – not least because a process called adaptive thermogenesis kicks in, which means our body goes into a power-saving mode because less energy is supplied through food.

In a new study involving mice, researchers think they've found a hormone-signaling pathway that might help. Signaling pathways are like biochemical chain reactions in the body, with particular triggers (such as drugs) leading to effects (such as weight loss).

In this case, the hormone growth differentiation factor 15 (GDF15) stopped mice from automatically lowering their energy use when they ate less, speeding up another metabolic process in their muscles.

"We have discovered that in mice, GDF15 blocks the slowing of metabolism that occurs during dieting by ramping up calcium futile cycling in muscle," says Gregory Steinberg, a medical scientist at McMaster University in Canada.

Previous research has established that GDF15 and its associated receptor GFRAL impact the amount of food mice will eat. Now researchers think it could help keep weight off in the longer term and help with dieting in the first place.

Read more here: https://www.sciencealert.com/scientist ... -burning

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American Gastroenterological Association Supports Reintroduction of Bipartisan Treat and Reduce Obesity Act
August 3 , 2023

Introduction:

(Eurekalert) Bethesda, MD (August 3, 2023) – The American Gastroenterological Association (AGA) today announced support for the reintroduced Treat and Reduce Obesity Act (TROA), which would expand Medicare coverage to include screening and treatment of obesity from a diverse range of health care providers who specialize in obesity care. The bill also includes coverage of behavioral counseling, prescription drugs for long-term weight management, and other prevention and treatment options.

“As gastroenterologists we see the chronic effects of obesity on patients’ health in conditions like metabolic dysfunction-associated fatty liver disease, formerly nonalcoholic fatty liver disease, and gastroesophageal reflux disease. Expanding access and improving early intervention and treatment options will help patients overcome these diseases and live healthier lives,” said Rotonya Carr, MD, Chair, AGA Government Affairs Committee. “Because many private insurance companies model their health benefits to reflect Medicare, the passage of TROA could lead to improved obesity care options for all Americans.”

We thank Sens. Tom Carper (D-DE) and Bill Cassidy (R-LA), and Reps. Brad Wenstrup (R-OH), Raul Ruiz (D-CA), Mariannette Miller-Meeks (R-IA) and Gwen Moore (D-WI) for their leadership on H.R. 4818/S. 2407, which is an important step to addressing obesity — a disease that affects 93 million Americans and could have an economic impact of $4.3 trillion annually if current trends continue.

Read more here: https://www.eurekalert.org/news-releases/997607

For AGA's obesity coverage advocacy toolkit: https://patient.gastro.org/obesity-cove ... -toolkit/

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[40lightyears]

Boosting liver mRNAs curbs appetite, body weight in obese mice

by University of Texas Health Science Center at San Antonio
https://medicalxpress.com/news/2022-04- ... etite.html

Scientists from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) today reported that inhibiting a liver enzyme in obese mice decreased the rodents' appetite, increased energy expenditure in adipose (fat) tissues and resulted in weight loss.

The finding, published in Cell Metabolism, provides a potentially desirable drug target to treat metabolic issues such as obesity and diabetes, the authors said.

"We first needed to discover this mechanism and, now that we have, we can develop drugs to improve metabolic syndrome," said senior author Masahiro Morita, Ph.D., assistant professor of molecular medicine in UT Health San Antonio's Sam and Ann Barshop Institute for Longevity and Aging Studies.

"We have an enzyme inhibitor that we want to make more specific to increase its effects," said first author Sakie Katsumura, DDS, Ph.D., postdoctoral fellow in the Morita laboratory.

The liver enzyme, called CNOT6L deadenylase, turns off messenger ribonucleic acids (mRNAs) that ordinarily carry genetic instructions from the nucleus to sites in the cell where two liver proteins are made.

One of the proteins, growth differentiation factor 15 (GDF15), sends signals to two regions of the hindbrain to control food intake. The other, fibroblast growth factor 21 (FGF21), sends signals to brown and white adipose tissues to increase energy expenditure. CNOT6L deadenylase impedes mRNA code-carrying for both GDF15 and FGF21, which reduces these benefits.

I often read these type of articles and I think a major problems is the food. In stores and restaurants is usually promoted directly or indirectly processed and fastfood.

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Drug that mimics exercise triggers weight loss and builds lean muscle
By Bronwyn Thompson
September 25, 2023

https://newatlas.com/medical/drug-mimic ... ight-loss/

As a new age of weight-loss therapeutics dawns, heralded by the likes of semaglutide (Ozempic, Wegovy), scientists are one step closer to creating a drug that can coax muscles into behaving as if they’ve just been put through a vigorous workout. Known as exercise mimetics, this proposed class of drugs essentially ‘mimics’ the benefits of exercise, triggering a mechanism that supercharges fat metabolism and encourages lean muscle mass.

"This compound is basically telling skeletal muscle to make the same changes you see during endurance training," said lead author Thomas Burris, professor of pharmacy at the University of Florida.

While exercise mimetics have been in the works for some time, the UF researchers found that a compound known as SLU-PP-332 was able to target a specific estrogen-related receptor (ERR), which boosted skeletal fat oxidation, therefore increasing energy expenditure.

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FDA approves a new weight loss drug, Zepbound from Eli Lilly

Source: CBS News

November 8, 2023 / 1:25 PM EST

The Food and Drug Administration approved a request by Eli Lilly on Wednesday to begin marketing its tirzepatide medication, which is branded as Mounjaro for diabetes, under a new brand for weight loss as well.

While Mounjaro had already been used by some patients "off-label" for weight loss, the new FDA approval will allow the drugmaker to begin officially selling and marketing tirzepatide — branded as Zepbound — for weight loss too. Zepbound will be available for patients in the U.S. by the end of the year, the drugmaker said.

The company said Wednesday in a news release that the medication will be sold at a cheaper list price than its semaglutide competitors from Novo Nordisk, which are branded as Wegovy for weight loss and Ozempic for diabetes.

"New treatment options bring hope to the many people with obesity who struggle with this disease and are seeking better options for weight management," Joe Nadglowski, CEO of the Obesity Action Coalition, said in Eli Lilly's release. The group receives funding from Eli Lilly and other pharmaceutical and health care companies.

Read more: https://www.cbsnews.com/news/fda-approv ... eli-lilly/

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Engineers develop a vibrating, ingestible capsule that might help treat obesity
https://medicalxpress.com/news/2023-12- ... esity.html
by Anne Trafton, Massachusetts Institute of Technology

When you eat a large meal, your stomach sends signals to your brain that create a feeling of fullness, which helps you realize it's time to stop eating. A stomach full of liquid can also send these messages, which is why dieters are often advised to drink a glass of water before eating.

MIT engineers have now come up with a new way to take advantage of that phenomenon, using an ingestible capsule that vibrates within the stomach. These vibrations activate the same stretch receptors that sense when the stomach is distended, creating an illusory sense of fullness.

The team's work is published in Science Advances.

In animals who were given this pill 20 minutes before eating, the researchers found that this treatment not only stimulated the release of hormones that signal satiety, but also reduced the animals' food intake by about 40%. Scientists have much more to learn about the mechanisms that influence human body weight, but if further research suggests this technology could be safely used in humans, such a pill might offer a minimally invasive way to treat obesity, the researchers say.

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Breakthrough as hugely promising weight-loss compound made in yeast
By Bronwyn Thompson
January 10, 2024
https://newatlas.com/medical/hugely-pro ... und-yeast/

A climbing vine known as the “Seven Steps of Death” holds within its toxic growth something scientists believe to be a powerful anti-obesity compound, celastrol. For the first time, this hotly touted compound has been produced simply and safely, using normal yeast as an ideal ‘surrogate' host.

The plant, better known as the thunder god vine (Tripterygium wilfordii), grows predominantly in China and has long been used in traditional medicine to treat rheumatoid arthritis, multiple sclerosis, Crohn’s disease, lupus, psoriasis, fever and more. But its toxicity to humans has made extracting its reportedly beneficial chemical properties time-consuming, risky and not at all scalable for further study and future commercial use.

Now, University of Copenhagen scientists have made the process of making celastrol simple and sustainable – the huge breakthrough needed to turn this promising compound into a viable, easily produced future obesity treatment.

"For obvious reasons, a person cannot just eat the plant and benefit from the drug,” said Sotirios Kampranis, professor at the Department of Plant and Environmental Sciences. “So what do we do? The problem with extracting celastrol from the nature source is that it is very hard to separate it from the other toxic molecules that the plant is full of. So far, there has been no effective method to achieve this.”

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No ‘easy’ weight loss: don’t overlook the social cost of anti-obesity drugs

https://www.nature.com/articles/d41586-024-00329-9