Obesity research, news and discussion thread

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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.

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Laser light, a dye and a nonsurgical implant could help overcome obesity
https://medicalxpress.com/news/2022-04- ... esity.html
by American Chemical Society

When dieting and exercise aren't enough, weight-loss surgery can be an effective obesity treatment. But people who don't want surgery have other options, including insertion of an appetite-suppressing balloon or other implant in the stomach. Now, researchers report in ACS Applied Materials & Interfaces that they have augmented that procedure in laboratory animals by coating an implant with a laser-activated dye that kills cells producing ghrelin, the "hunger hormone."

Implants can be inserted in the stomach through the mouth after local anesthesia. In 2019, Hwoon-Yong Jung, Jung-Hoon Park and colleagues designed a new type of implant. The "intragastric satiety-inducing device" (ISD) consists of a stent — which lodges in the lower esophagus — attached to a disk that rests in the opening to the stomach. The disk has a hole in the center to let food through. Tests in pigs showed that the ISD lowered food intake and weight gain by enhancing the feeling of fullness and reducing levels of ghrelin, which is produced by cells near the top of stomach. But the device caused complications, including acid reflux and migration into the stomach. In their latest project, Jung, Park, Kun Na and colleagues wanted to find out if they could suppress ghrelin even more by coating the ISD's disk with a compound that, with a shot of laser light, could kill some of the ghrelin-producing cells. The implant could then be removed to avoid the side effects associated with the initial design.

[weatheriscool]

Researchers have uncovered a regulator of body weight that could lead to new treatments for metabolic disorders
https://medicalxpress.com/news/2022-04- ... bolic.html
by Yale University

Yale scientists have discovered that a protein known as augmentor-alpha regulates body weight in mice, an insight that could lead to new treatments for metabolic disorders.

The findings were published April 11 in the Proceedings of the National Academy of Sciences.

The research team decided to take a closer look at augmentor-alpha because of its connection to cancer. The protein is known to bind to and activate the anaplastic lymphoma kinase receptor (ALK), a molecule that when mutated, drives a variety of human cancers, including pediatric neuroblastoma, B-cell lymphomas and certain lung cancers.

To better understand this protein and the role it plays in the body, Yale researchers first wanted to pinpoint where it is commonly located. Looking in mice, they found that augmentor-alpha was most strongly expressed in the hypothalamus region of the brain.

In particular, they found it was expressed within cells called agouti-related peptide (AgRP) neurons, which are known to promote hunger.

[weatheriscool]

Elon Musk said his Neuralink brain chip could help treat morbid obesity. Scientists say it's a long
shot – but not an impossibility.

Elon Musk believes his Neuralink brain chip could help treat morbid obesity. Experts say the billionaire's dream isn't as far-fetched as it may seem.

"I don't think it is any more implausible than other claims for the potential of neurotechnology," Professor Andrew Jackson, an expert in neural interfaces at Newcastle University, told Insider.

Musk made the suggestion in a TED interview on April 14, thereby adding "morbid obesity" to a growing list of ailments he believes Neuralink could help treat.

Experts interviewed by Insider said a commercially-available obesity-busting brain chip was a long way off but the concept was promising if backed by the right science.

https://www.yahoo.com/news/elon-musk-sa ... 00779.html

[Nanotechandmorefuture]

Elon Musk said his Neuralink brain chip could help treat morbid obesity. Scientists say it's a long
shot – but not an impossibility.

Elon Musk believes his Neuralink brain chip could help treat morbid obesity. Experts say the billionaire's dream isn't as far-fetched as it may seem.

"I don't think it is any more implausible than other claims for the potential of neurotechnology," Professor Andrew Jackson, an expert in neural interfaces at Newcastle University, told Insider.

Musk made the suggestion in a TED interview on April 14, thereby adding "morbid obesity" to a growing list of ailments he believes Neuralink could help treat.

Experts interviewed by Insider said a commercially-available obesity-busting brain chip was a long way off but the concept was promising if backed by the right science.

https://www.yahoo.com/news/elon-musk-sa ... 00779.html

Lol! He really wants people to put those brain chips in them early on. There is a motorcycle cop that got in a crash not too long ago here in Miami, Fl. That sounds like a good candidate and many more if they are looking for legit people who could be interested. I say that because the other selling point of Neuralink was neck and spine issues.

[Tadasuke]

In 2010, when I was wildly optimistic, I wrote predictions for 2015, 2020, 2025 and 2030 for many areas, including dealing with obesity.
Citing from my notes:
"In the year 2015 there is a new drug, which completely solves the problem of obesity, by not allowing human metabolism to store more fat than necessary. Because it just became available after decades of research, it's expensive and not many people benefit from it right away. In recent years, it was accelerated and developed with the help of petascale supercomputers and AI.
In the year 2020, anti-obesity drugs are cheap, mass produced and widely available. Obesity is a problem of the past, there's no more such an issue as being overweight. Everyone is slim and healthier. Happiness levels are improving worldwide, partially because of it."

In reality instead of what I wrote, we are seeing this kind of "progress":


Truly very depressing. In my country there's an increasingly bigger problem with obesity, I see more and more obese people and at the same time, more and more people who go to the gym or run. It's weird. I am not overweight, but I feel sad every time I see someone overweight. I think that normalizing obesity is wrong and unhealthy. I wanted us to seek perfection, not accept that we are shit.

[peekpok]

As someone who struggles with their weight I feel that the root of the problem for most is food addiction. Exercise helps of course, but realistically the only way to lose weight reliably is through caloric restriction. It's easy in theory but not in practice. I can notice a palpable, negative difference in my mental health when I am eating at a deficit. Food really does help people cope with their troubles in life, unfortunately it causes other troubles.

[SerethiaFalcon]

I would add it is also a vicious feedback loop. As your body adjusts to the new normal, it thinks you are starving when you try to restrict your caloric intake, making it harder to keep to the caloric restriction. Starvation is a positive sensation in nature for survival, but it surely doesn't help people that want or need to lose weight for health. There is something I stumbled upon that is a different approach, where you restrict caloric intake to different amounts each day making it easier to lose weight and not plateau, but the starvation reaction of the body would still be difficult to manage. I'm experimenting with it myself, but it is difficult to make headway.

As far as weight goes, while calories and exercise are the main contributors, I still theorize that there are other factors that can make things worse. Certain hormone disorders, at least in women, cause problems with certain types of food, which means weight can be more challenging to keep off, as more foods have to be avoided to be successful (lest the hormones affected by certain foods get out of control). Drugs for mental health are still something that is poorly studied, in my opinion, and I have seen so much weight gain from people being on them. The worst offenders are antipsychotics, and I'm not sure if they have tested what happens if they put someone on them that was misdiagnosed. It does happen, especially with overzealous psychiatrists and hospital environments where they quickly diagnose people instead of taking the time to figure out things (and with the overlap of symptoms in so many disorders). These types of drugs can significantly affect appetite, for things like antidepressants, it is probably due to feeling better, but antipsychotics are a different story. They severely mess with your body, especially the digestive system etc. They can even cause heart palpitations in some people. I also have an odd theory that if you go from a society with little processed food to a society with highly processed food, the gut microbiome is badly affected, which could also change how the body responds to food, perhaps. It's unproven, just a thought process of mine. This is probably even worse if antibiotics are used too, as that tends to wipe out your microbiome anyway. Of course, there are the more commonly known problems like thyroid issues and genetics too. These are just added factors that contribute to the difficulty of losing weight for some people.

[Tadasuke]

This may perhaps also be a factor in obesity:

[weatheriscool]

Mapping brain stem's control of eating could lead to better treatments for obesity
https://medicalxpress.com/news/2022-08- ... esity.html
by Kelly Malcom, University of Michigan

Every meal you sit down to makes an impression, with foods filed away as something delicious to be sought out again, or to be avoided in disgust if we associate the flavor with gut malaise.

How this decision is made turns out to be so fundamental to our well-being—determining what foods to seek and avoid—that the signals are coordinated within the most primitive parts of our brains, the brain stem or hindbrain. This brain region also helps us decide when we are "full" and should stop eating.

To date, scientists interested in how and why people gain weight and the diseases that can result from overeating and obesity have focused on a part of the brain called the hypothalamus, following discoveries of two intertwined systems that play important roles in controlling energy balance, the leptin and melanocortin systems.

[weatheriscool]

Deep brain stimulation promising against binge eating disorder
https://medicalxpress.com/news/2022-08- ... order.html
by University of Pennsylvania

A small device that detects food craving-related brain activity in a key brain region, and responds by electrically stimulating that region, has shown promise in a pilot clinical trial in two patients with loss-of-control binge eating disorder (BED), according to researchers at the Perelman School of Medicine at the University of Pennsylvania.

The trial, described in a paper that appears today in Nature Medicine, followed the two patients for six months, during which the implanted device—of a type normally used to treat drug-resistant epilepsy—monitored activity in a brain region called the nucleus accumbens. The nucleus accumbens is involved in processing pleasure and reward, and has been implicated in addiction. Whenever the device sensed nucleus accumbens signals that had been found to predict food cravings in prior studies, it automatically stimulated that brain region, disrupting the craving-related signals. Over six months of treatment, the patients reported far fewer binge episodes, and lost weight.

"This was an early feasibility study in which we were primarily assessing safety, but certainly the robust clinical benefits these patients reported to us are really impressive and exciting," said study senior author Casey Halpern, MD, an associate professor of Neurosurgery and chief of Stereotactic and Functional Neurosurgery at Penn Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center.

[peekpok]

Deep brain stimulation seems like a miraculous technology but I've heard there are issues with the longevity of the implants.

[weatheriscool]

Insufficient insulin processing leads to obesity
https://medicalxpress.com/news/2022-09- ... esity.html
by University of Basel

Obesity increases the risk of an imbalance in sugar metabolism and even of diabetes. A research group at the University of Basel has now shown the opposite is true as well: deficits in the body's insulin production contribute to obesity.

Poor nutrition, too little movement and too many pounds on the scale—lifestyle influences the risk of metabolic diseases like diabetes. But the relationship works the other way around as well, as a research group led by Dr. Daniel Zeman-Meier of the university's Department of Biomedicine and the University Hospital of Basel reports. If insulin production is compromised, as is the case in the early stages of type 2 diabetes, this can contribute to obesity. The researchers report their findings in the journal Nature Communications.

The research team focused on protease PC1/3, a key enzyme in the body that transforms various inactive hormone precursors into the final, active forms. If this enzyme isn't functioning properly in a person, the result can be severe endocrine disorders. The consequences include a feeling of uncontrollable hunger and severe obesity.

"Until now, it was assumed that this dysregulation is caused by a lack of activation of satiety hormones," explains the study's leader, Dr. Zeman-Meier. "But when we turned off PC1/3 in the brains of mice, the animals' body weight did not change significantly." The researchers concluded from this that something other than a brain malfunction must be responsible.

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Scientists redefine obesity with discovery of two major subtypes
https://medicalxpress.com/news/2022-09- ... major.html
by Van Andel Research Institute

A team led by Van Andel Institute scientists has identified two distinct types of obesity with physiological and molecular differences that may have lifelong consequences for health, disease and response to medication.

The findings, published today in the journal Nature Metabolism, offer a more nuanced understanding of obesity than current definitions and may one day inform more precise ways to diagnose and treat obesity and associated metabolic disorders.

The study also reveals new details about the role of epigenetics and chance in health and provides insights into the link between insulin and obesity.

"Nearly 2 billion people worldwide are considered overweight and there are more than 600 million people with obesity, yet we have no framework for stratifying individuals according to their more precise disease etiologies," said J. Andrew Pospisilik, Ph.D., chair of Van Andel Institute's Department of Epigenetics and corresponding author of the study. "Using a purely data-driven approach, we see for the first time that there are at least two different metabolic subtypes of obesity, each with their own physiological and molecular features that influence health. Translating these findings into a clinically usable test could help doctors provide more precise care for patients."

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Scientists identify drug that mimics effects of exercise on muscle and bone
https://medicalxpress.com/news/2022-09- ... uscle.html
by Tokyo Medical and Dental University

Maintaining a regular workout routine can help you look and feel great—but did you know that exercise also helps maintain your muscles and bones? People who are unable to engage in physical activity experience weakening of the muscles and bones, a condition known as locomotor frailty. Recently, researchers in Japan have identified a new drug that may aid in the treatment of locomotor frailty by inducing similar effects as exercise.

Physical inactivity can result in a weakening of the muscles (known as sarcopenia) and bones (known as osteoporosis). Exercise dispels these frailties, increasing muscle strength and promoting bone formation while suppressing bone resorption. However, exercise therapy cannot be applied to all the clinical cases. Drug therapy may be helpful in treating sarcopenia and osteoporosis, especially when the patients have cerebrovascular disease, dementia or when they have already become bedridden. However, there is no single drug that addresses both issues simultaneously.

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Researcher discovers a muscle that can promote glucose and fat burning to fuel metabolism for hours while sitting

by Laurie Fickman, University of Houston
https://medicalxpress.com/news/2022-09- ... olism.html

From the same mind whose research propelled the notion that "sitting too much is not the same as exercising too little," comes a groundbreaking discovery set to turn a sedentary lifestyle on its ear: The soleus muscle in the calf, though only 1% of your body weight, can do big things to improve the metabolic health in the rest of your body if activated correctly.

And Marc Hamilton, professor of Health and Human Performance at the University of Houston, has discovered such an approach for optimal activation—he's pioneering the "soleus pushup" (SPU) which effectively elevates muscle metabolism for hours, even while one is sitting. The soleus, one of 600 muscles in the human body, is a posterior leg muscle that runs from just below the knee to the heel.

Published in the journal iScience, Hamilton's research suggests the soleus pushup's ability to sustain an elevated oxidative metabolism to improve the regulation of blood glucose is more effective than any popular methods currently touted as a solution including exercise, weight loss and intermittent fasting. Oxidative metabolism is the process by which oxygen is used to burn metabolites like blood glucose or fats, but it depends, in part, on the immediate energy needs of the muscle when it's working.

"We never dreamed that this muscle has this type of capacity. It's been inside our bodies all along, but no one ever investigated how to use it to optimize our health, until now," said Hamilton. "When activated correctly, the soleus muscle can raise local oxidative metabolism to high levels for hours, not just minutes, and does so by using a different fuel mixture."

[weatheriscool]

Scientists propose that obesity is a neurodevelopmental disorder
https://medicalxpress.com/news/2022-09- ... order.html
by Baylor College of Medicine

Obesity has increased rapidly in recent decades to affect more than 2 billion people, making it one of the largest contributors to poor health worldwide. Despite decades of research on diet and exercise treatments, many people continue to struggle to lose weight. Researchers at Baylor College of Medicine and collaborating institutions now think they know why, and say we must shift the focus from obesity treatment to prevention.

The team reports in the journal Science Advances that molecular mechanisms of brain development during early life are likely a major determinant of obesity risk. Previous large studies in humans have hinted that genes that are most strongly associated with obesity are expressed in the developing brain. This current study in mice focused on epigenetic development. Epigenetics is a system of molecular bookmarking that determines which genes will, or will not, be used in different cell types.

"Decades of research in humans and animal models have shown that environmental influences during critical periods of development have a major long-term impact on health and disease," said corresponding author Dr. Robert Waterland, professor of pediatrics-nutrition and a member of the USDA Children's Nutrition Research Center at Baylor. "Body weight regulation is very sensitive to such 'developmental programming,' but exactly how this works remains unknown."

"In this study we focused on a brain region called the arcuate nucleus of the hypothalamus, which is a master regulator of food intake, physical activity and metabolism," said first author Dr. Harry MacKay, who was a postdoctoral associate in the Waterland lab while working on the project. "We discovered that the arcuate nucleus undergoes extensive epigenetic maturation during early postnatal life. This period is also exquisitely sensitive to developmental programming of body weight regulation, suggesting that these effects could be a consequence of dysregulated epigenetic maturation."

[weatheriscool]

Major obesity advance takes out targeted fat depots anywhere in the body
By Nick Lavars
December 01, 2022
https://newatlas.com/medical/charged-na ... MAIL_ID%5D

The fat cells of an elite athlete can appear quite different to those in an obese subject, and technologies that make one function more like the other could unlock powerful new therapies for the condition. Scientists are reporting an exciting advance in this field, demonstrating how positively-charged nanomaterials can be injected into unhealthy fat to return it to a healthy state, laying the foundation for treatments that selectively target fat depots anywhere in the body.

Led by scientists at Columbia University, the research was published across two papers and centers on the different functions fat cells can take on in the human body, and the difference between healthy fat metabolism and unhealthy fat formation. Fat cells store energy in the form of lipids, but when they're tasked with taking on too much, they start to grow large and undergo changes to specific genes, ultimately leading to obesity.

The research team set out to remodel these fat cells rather than simply destroy them, and have found success using a positively charged nanomaterial called PAMAM generation 3 (P-G3). The scientists were inspired to deploy P-G3 against fat cells after finding that some fat tissue contains a negatively charged extracellular matrix (ECM), the support structure for the cells. This raised the possibility that the ECM could act as a transport system for positively charged molecules.

So, the team injected P-G3 into obese mice and indeed found that it spread rapidly throughout the fat tissue. They were surprised to find, however, that the nanomaterial had the effect of shutting down the lipid storage function of the fat cells, effectively returning them to a younger, healthier state. The mice lost weight as a result.

“With P-G3, fat cells can still be fat cells, but they can't grow up,” said study author Kam Leon. “Our studies highlight an unexpected strategy to treat visceral adiposity and suggest a new direction of exploring cationic nanomaterials for treating metabolic diseases.”

[weatheriscool]

Dozens of brain proteins may play a critical role in body weight regulation
https://medicalxpress.com/news/2023-04- ... tical.html
by Laval University

Genetic factors could contribute to up to 50%–75% of the variance in body mass index, or BMI, in the population.

By analyzing the genome of more than 800,000 people of European descent, a research team from Université Laval and the Quebec Heart and Lung Institute Research Center has identified 60 unique proteins expressed in the brain that may be critical regulators of body weight.

This study explored the link between genetic regions associated with body weight and the proteins expressed in the brain. "Previous study showed that hundreds of genetic regions influence body weight. In most cases, the function of these genes remains unknown. Our study reports that about 60 of these genes encode proteins that could influence body weight via their expression in the brain," says Éloi Gagnon, a doctoral student in clinical and biomedical sciences at the Université Laval Faculty of Medicine and first author of the study published in iScience.

[weatheriscool]

Study findings could pave the way for development of new strategies to prevent and treat obesity
https://medicalxpress.com/news/2023-04- ... esity.html
by University of Nottingham

New research has shown that weight loss, or bariatric, surgery can significantly alter the levels of bile acid associated with higher appetite, as can taking fiber supplements but to a lesser degree.

Bariatric surgery can be used as a treatment for people who are very obese and there are several types of surgery available, such as reducing the size of the stomach or rerouting the top part of the stomach to the small intestine. It's an invasive procedure but can lead to significant improvements in weight loss, metabolic health, and a reduction in appetite—though the reasons for this are unknown. Bile acids are a marker of poor cardiometabolic health that can affect liver function and inflammation.

A study, published today in Cell Reports Medicine by researchers from the University of Nottingham, King's College London and Amsterdam University Medical Center, has shed light on the molecules underlying the benefits of this kind of surgery on patient appetite and metabolism.

Researchers studied a group of patients in Amsterdam who had undergone bariatric surgery by measuring levels of bile acids before surgery and a year post-operation. They also studied bile acids from two population studies—TwinsUK, run by King's College London, and PREDICT, run by King's College London and nutrition company ZOE.

The study found that a specific bile acid called isoursodeoxycholate (isoUDCA), which is associated with higher appetite and worse metabolic levels, decreased after bariatric surgery and after taking fiber supplements. Levels of isoUDCA did not decrease after consuming omega-3 supplements.

Joint lead author Professor Ana Valdes from the University of Nottingham's School of Medicine said, "Bariatric surgery is not only extremely effective at helping people lose weight by reducing their appetite, but also improves their liver function and their metabolism."