Global Ozempic shortage fix: Cheaper, faster method produces 10x more
By Paul McClure
March 12, 2024
https://newatlas.com/medical/novel-semaglutide-analog/
Manufacturing the groundbreaking and extremely popular diabetes and weight-loss drug semaglutide – Ozempic, Wegovy – is a complex, slow process. Amid ongoing global shortages, researchers have developed a cheaper, faster method that produces ten times more of a therapeutically similar version of the in-demand drug.
The effectiveness of semaglutide, sold as the diabetes drug Ozempic and weight-loss drug Wegovy, contributed to its overwhelming popularity and huge demand. This led to global shortages throughout 2022–23, which maker Novo Nordisk says will likely continue into this year. The shortage has particularly affected type 2 diabetics who rely on semaglutide to keep their blood glucose levels under control and are left searching for suitable alternatives.
Researchers at The Florey Institute in Melbourne, Australia, may have discovered a way of addressing the critical shortage, developing a method of production of a drug analog that has the same therapeutic effects as semaglutide. Their novel production method is not only cost-effective and simpler but produces far more of the drug.
An "anti-hunger" molecule produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin, according to a new study in mice and humans. The molecule, lac-phe, was discovered by Stanford Medicine researchers in 2022.
The finding, made jointly by researchers at Stanford Medicine and at Harvard Medical School, further cements the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite. It may pave the way to a new class of weight loss drugs.
"Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear," said Jonathan Long, Ph.D., an assistant professor of pathology. "Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people."
Long and Mark Benson, MD, Ph.D., an assistant professor of medicine at Harvard Medical School, are co-senior authors of the study, which was published in Nature Metabolism. Postdoctoral scholar Shuke Xiao, Ph.D., is the lead author of the study.
Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide drugs such as Ozempic and Wegovy, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.
Post-workout appetite loss
When Long and colleagues at Baylor University discovered lac-phe in 2022, they were on the hunt for small molecules responsible for curtailing hunger after vigorous exercise. What they found was a Frankenbaby of lactate—a byproduct of muscle fatigue—and an amino acid called phenylalanine. They dubbed the hybrid molecule lac-phe and went on to show that it's not only more abundant after exercise but it also causes people (as well as mice and even racehorses) to feel less hungry immediately after a hard workout.
Kombucha microbes break down fat stores like fasting – without the effort
By Bronwyn Thompson
April 03, 2024
It may not be to everyone's taste, but kombucha tea may be able to deliver the benefits of fasting, without the hardest part – the fasting itself. Researchers found that the when the yeasts and bacteria from the fermented, sweetened tea colonized the gut, they altered fat metabolism, without any other dietary changes, resulting in lower fat stores.
At the center of these findings is the flora found in kombucha tea's SCOBY (Symbiotic Cultures of Bacteria and Yeasts), the gelatinous starter, rich in microbes, found floating near the surface of the fermented liquid. The probiotic microbes, including species of Acetobacter, Lactobacillus and Komagataeibacter genera, have previously been linked to a range of positive health benefits including lowering blood pressure.
A study led by Medical Research Council (MRC) researchers has identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date.
The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.
The study, published in Nature Genetics, was led by researchers at the MRC Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the University of Cambridge.
Brown fat, also known as brown adipose tissue (BAT), is a type of fat in our bodies that's different from the white fat around our belly and thighs that we are more familiar with. Brown fat has a special job—it helps to burn calories from the foods that we eat into heat, which can be helpful, especially when we're exposed to cold temperatures like during winter swimming or cryotherapy.
For a long time, scientists thought that only small animals like mice and newborns had brown fat. But new research shows that a certain number of adults maintain their brown fat throughout life. Because brown fat is so good at burning calories, scientists are trying to find ways to activate it safely using drugs that boost its heat-producing abilities.
A new study published in Nature Metabolism from the research groups of Prof. Jan-Wilhelm Kornfeld from the University of Southern Denmark/the Novo Nordisk Center for Adipocyte Signaling (Adiposign) and Dagmar Wachten from the University Hospital Bonn and the University of Bonn (Germany) has found that brown fat has a previously unknown built-in mechanism that switches it off shortly after being activated. This limits its effectiveness as treatment against obesity.
The current breakthrough weight-loss drugs are only the beginning, according to Danish researchers hard at work on a new treatment that targets the brain's natural plasticity, which could offset bad side effects and provide more long-term benefits.
“I consider the drugs available on the market today as the first generation of weight-loss drugs," said Christoffer Clemmensen, Associate Professor at the Novo Nordisk Foundation Center for Basic Metabolic Research, at the University of Copenhagen, and senior author of the study. "Now we have developed a new type of weight-loss drug that affects the plasticity of the brain and appears to be highly effective.”
Where current GLP-1 drugs mimic the natural hormonal response following eating, signaling 'fullness' and slowing the emptying of the stomach, the new treatment instead uses GLP-1 peptide to "smuggle" molecules across the blood-brain barrier and into the appetite control center, to then block the NMDA receptor protein. This receptor has previously gained interest among researchers for its ability to aid in changing up brain connections to aid learning and memory. And unlike what's currently on the market, this new approach could harness the brain's plasticity to cement new pathways in its appetite center – pathways that would remain in place long after treatment had ceased.
“What is spectacular – on a cellular level – about this new drug is the fact that it combines GLP-1 and molecules that block the NMDA receptor," said researcher Jonas Petersen, the study's first author and the chemist who synthesized the molecules. "It exploits GLP-1 as a Trojan Horse to smuggle these small molecules exclusively into the neurons that affect appetite control. Without GLP-1, the molecules that target the NMDA receptor would affect the entire brain and thus be non-specific.”
In a study published in Nature, Christoffer Clemmensen and colleagues demonstrate a new use of the weight loss hormone GLP-1. GLP-1 can be used as a "Trojan Horse" to smuggle a specific molecule into the brain of mice, where it successfully affects the plasticity of the brain and results in weight loss.
"I consider the drugs available on the market today as the first generation of weight-loss drugs. Now we have developed a new type of weight-loss drug that affects the plasticity of the brain and appears to be highly effective," says Clemmensen, from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen and senior author of the study.
"The effect of GLP-1 combined with these molecules is very strong. In some cases, the mice lose twice as much weight as mice treated with GLP-1 only."
Weight-loss breakthrough easily hacks white fat to turn calorie-burning beige
By Bronwyn Thompson
July 01, 2024
By suppressing just one protein, stores of white fat can switch to becoming calorie-burning beige fat, in a feat that so far has eluded scientists working on this long-studied area of obesity treatment.
University of California San Francisco researchers found that by suppressing the protein KLF-15 – which they'd earlier identified as playing a role in cell metabolism, and one that is far more abundant in calorie-burning beige and brown fat – the cells themselves switched their function.
And without the protein present, the default setting for fat cells appeared to be beige, not the predominant white.
“A lot of people thought this wasn’t feasible,” said Brian Feldman, MD Distinguished Professor in Pediatric Endocrinology and senior author of the study. “We showed not only that this approach works to turn these white fat cells into beige ones, but also that the bar to doing so isn’t as high as we’d thought.”
Previously, scientists had focused on turning stem cells into calorie-burning brown or beige fat, which is essentially used by our bodies as fuel for temperature regulation. As such, these cells burn through fat stores, whereas white adipose tissue are the stores we find so hard to shift in weight loss.
weatheriscool wrote: ↑Mon Jul 01, 2024 3:31 pm
Weight-loss breakthrough easily hacks white fat to turn calorie-burning beige
By Bronwyn Thompson
July 01, 2024
By suppressing just one protein, stores of white fat can switch to becoming calorie-burning beige fat, in a feat that so far has eluded scientists working on this long-studied area of obesity treatment.
University of California San Francisco researchers found that by suppressing the protein KLF-15 – which they'd earlier identified as playing a role in cell metabolism, and one that is far more abundant in calorie-burning beige and brown fat – the cells themselves switched their function.
And without the protein present, the default setting for fat cells appeared to be beige, not the predominant white.
“A lot of people thought this wasn’t feasible,” said Brian Feldman, MD Distinguished Professor in Pediatric Endocrinology and senior author of the study. “We showed not only that this approach works to turn these white fat cells into beige ones, but also that the bar to doing so isn’t as high as we’d thought.”
Previously, scientists had focused on turning stem cells into calorie-burning brown or beige fat, which is essentially used by our bodies as fuel for temperature regulation. As such, these cells burn through fat stores, whereas white adipose tissue are the stores we find so hard to shift in weight loss.
The next chapter in the story of headline-making popular obesity drugs may center on the physiological relationship between feeling satisfied after a meal versus the neurological control of nausea. By teasing apart the therapeutic benefits from the adverse effects of these medications, researchers from the Monell Chemical Senses Center found a population of neurons in the brain that controls food intake without causing nausea in an animal model.
The study, published in the journal Nature, describes two distinct neural circuits that govern different effects of the same drug. The drugs studied are among the most effective weight-loss drugs available—known as long-acting glucagon-like peptide-1 receptor (GLP1R) agonists—which initiate neurochemical responses via receptors expressed in the body.
Majority in UK want new tax on makers of ultra-processed and junk food
Sun 11 Aug 2024 14.00 BST
A majority of people in Britain want new taxes imposed on companies that make either junk food or ultra-processed foodstuffs to help tackle the obesity crisis, polling suggests.
The findings prompted calls for ministers to help people eat healthier diets by putting a sugar tax-style levy on sweets, cereals, pizzas and other products containing too much salt or sugar.
In a survey by Ipsos for the Health Foundation thinktank, 58% of those questioned said they backed the introduction of a tax on organisations that produce foods high in sugar or salt, with some of the revenue to be used to buy fresh fruit and vegetables for poor families.
Ipsos found that a smaller proportion of people, but still a majority (53%) favoured imposing a tax on companies that produce ultra-processed food, such as ham, biscuits and mass-produced bread, with some of the proceeds raised to be deployed to help low-income households eat better.
On taxing junk food producers, only 19% of the representative sample of 2,136 UK adults were opposed to the idea and 20% said they did not know. A larger number (24%) were opposed to ultra-processed food manufacturers facing taxes while 21% did not know.
Force food firms to disclose products’ health ratings, industry boss urges
Mon 28 Oct 2024 05.00 GMT
Food firms should be forced to reveal how healthy or unhealthy their products are, to help people consume a better diet, an industry boss has said.
Ministers should compel companies to publish an annual report so consumers can see how much of their sales is made up of dishes that contain too much fat, salt and sugar, Stéfan Descheemaeker also said.
Descheemaeker is the chief executive of Nomad Foods, which owns popular brands such as Birds Eye fish fingers, Findus frozen foods and Goodfella’s pizzas.
He told the Guardian that mandatory publication of what proportion of each firm’s sales count as healthy or unhealthy under government guidelines would kickstart a “nutrition arms race” in which manufacturers would vie with each other to make their products better for health.
He also urged Wes Streeting, the health secretary, to ensure that all tins and packets of foodstuffs carry traffic light-style labels. This would also help tackle the obesity crisis because it would encourage people to choose more nutritious foods and shun less healthy options, he said.
Inflated balloons that trick the stomach into feeling full have long been used for weight loss. The problem is that they become less effective the longer they stay inflated. Now, MIT engineers have devised a balloon that inflates and deflates on demand – and it reduced food intake by 60%.
It’s trite to say that obesity is a global problem that contributes to the morbidity and mortality of millions. The widespread popularity of injectable anti-obesity medications would seem to indicate that many people already know this. However, those who can’t take these drugs because of their side effects or expense need an effective weight loss alternative.
An inflated balloon that occupies stomach space, producing a continuous feeling of fullness to curb overeating, is not a new weight loss method. However, the effectiveness of this approach can wane over time because the balloon is always inflated. Now, MIT engineers have outlined in a new study how they’ve devised a gastric balloon that can be inflated and deflated as needed.
Obesity rate among US adults fell in 2023 for first time in over a decade: Study
Source: The Hill
12/14/24 12:13 PM ET
The obesity rate among U.S. adults fell in 2023 for the first time in over a decade, according to a new study released on Friday.
The study published in the journal JAMA Health Forum found that obesity nationwide has dropped from 46 percent in 2022 to 45.6 percent last year. The researchers also discovered that obesity has declined substantially in the South, including among women older adults, ages 66 to 75.
“In the U.S overall, obesity was on the decline, led by the South, but in some regions that weren’t the case,” computational epidemiologist Benjamin Rader and the study’s author told NBC News. “We also saw large drops among Black Americans, but we saw increases in obesity among Asian Americans,” he added.
The study was conducted with over 16.7 million adults from 2013 to 2023. The authors looked at people from different age groups, races, sexes, ethnicities and regions. The researchers examined body mass index (BMI) figures that were observed from people’s health records.
Shaped by fads and one-size-fits-all approaches, current dietary practices rely on the idea that everyone needs the same food to achieve similar results, an idea challenged by new research from the University of Virginia.
UVA medical researchers say genetic background has a more prominent impact on body weight, fat mass, blood sugars and lipids than specific diets. Researchers fed four different diets with similar macronutrient content to four genetically diverse groups of mice.
The diets were Mediterranean, vegetarian and vegan diets, in addition to the "typical American diet" commonly associated with negative health outcomes.
"People with weight issues often feel like they are eating the same thing as others who are close to them, but not getting the same results," said Dr. Heather Ferris, associate professor of medicine and physician–scientist with a specialty in diabetes management. "It is likely individuals' genetics is at play."
Weight-loss breakthrough as new appetite-curbing hormone is found
By Bronwyn Thompson
January 29, 2025
https://newatlas.com/disease/obesity/ob ... dy-raptin/
A brand new candidate for weight-loss treatment is on the table, with scientists uncovering for the first time how a hormone produced by the hypothalamus during sleep has a direct impact on appetite regulation and metabolism. This opens the door to developing a novel class of medication that could tackle obesity like GLP-1 agonists.
"Sleep deficiency is associated with obesity, but the mechanisms underlying this connection remain unclear," the Chinese scientists noted in the study. "Here, we identify a sleep-inducible hypothalamic protein hormone in humans and mice that suppresses obesity. This hormone is cleaved from reticulocalbin-2 (RCN2), and we name it raptin."
Researchers from the Xiangya Hospital of Central South University have become the first to identify and understand how this sleep-induced hypothalamic hormone signals satiety to the gut, curbing food intake. What's more, poor or inadequate sleep greatly reduces raptin levels, which blocks appetite control. And raptin levels were much lower in those with obesity.
Gold outperforms Ozempic for weight loss – and leaves muscles alone
By Bronwyn Thompson
February 10, 2025
There's a growing body of evidence that gold nanoparticles can offer significant, targeted weight loss that focuses on fat (lipid) tissue, without affecting muscle structure. What's more, there are added health bonuses, including anti-inflammatory properties and improvements in blood glucose levels.
Scientists from Egypt's Alexandria University have furthered what we know about gold nanoparticles (AuNPs), demonstrating that weekly doses have the potential to lead to significant weight loss – perhaps even more than the GLP-1 class of medications – and, unlike those drugs, showed no evidence of muscle wastage.
New weight loss mechanism blocks formation of white fat cells in mice
By Michael Irving
February 27, 2025
Scientists in China have found a new potential drug target for weight loss. Blocking a protein called CD44 has been shown to protect against obesity in mice on a high-fat diet, specifically by suppressing the formation of white fat cells.
Semaglutide medications like Ozempic were originally approved to treat type 2 diabetes, but weight loss was noticed as a nice bonus, since it functions as an appetite suppressor. Other versions of semaglutide drugs, like Wegovy, were later approved to specifically treat obesity. Unfortunately they seem to have their share of side effects, including muscle loss and increased risk of a rare form of blindness.
