Sat, May-04-24, 14:10
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Plan: Muscle Centric
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Location: UK
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How 'switching on' brown fat may protect against obesity
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How 'switching on' brown fat may protect against obesity
- More than 1 billion people globally are obese.
- Scientists predict that the number of people living with obesity around the world will hit 4 billion by 2050.
- Researchers from Southern Danish University in Denmark have found that activating healthy ‘brown fat’ in the body may help protect against obesity, via a mouse model.
Recent research states that more than 1 billion people around the world have obesity, with scientists projecting that number may hit 4 billion by 2050.
As obesity can harm a person’s overall health and increase their risk for many diseases, researchers continue to find ways to fight the condition.
Case in point — researchers from Southern Danish University in Denmark have found via a mouse model that activating healthy brown fat in the body may help protect against obesity.
The study was recently published in the journal Nature Metabolism
What is brown fat?
Humans and other mammals have two main types of fat in the body — white fat and brown fat.
“White fat is an organ that stores calories from foods and whose size expands in obesity and causes medical problems,” Jan-Wilhelm Kornfeld, PhD, professor and co-founder of the Novo Nordisk Foundation Center for Adipocyte Signaling (Adiposign) in the Department of Biochemistry and Molecular Biology at Southern Danish University, co-lead author of the current study, explained to Medical News Today.
“Brown fat stores only little amounts of fat, but in contrast can convert calories from food into heat which is thereby ‘lost’ for the body,” he noted.
“Uniquely, activation of brown fat can lead to turning over calories from food which is beneficial in obesity and cardiometabolic diseases,” Kornfeld added. “White fat is much less able to do so.”
Activating brown fat protects against obesity in animal models
For this study, Kornfeld and his team focused on a protein called AC3-AT, which they found was responsible for “switching off” brown fat activation.
“AC3-AT is a new protein uniquely ‘made’ in brown fat when you activate brown fat, e.g. by cold exposure of mice and humans,” Kornfeld detailed. “It helps to ‘shut down’ the beneficial properties of brown fat — increase calorie usage and metabolic activation. Strategies aiming to inactivate AC3-AT might thus release this ‘break’ of brown fat activation and make brown fat active for longer times.”
Researchers used a mouse model to test their theory. They found that mice who had AC3-AT removed from their genome were protected from obesity, as their bodies were better at burning calories and their metabolism sped up due to brown fat activation.
“In principle, this shows that inactivation of AC3-AT can lead to weight loss (and) improvement of metabolic health in obesity,” Kornfeld said. “One would use other approaches in people — antibodies, RNA-based medicines, [and] small molecules.”
“I think that AC3-AT is only the ‘tip of the iceberg’ and that we can find many additional cold-inducible proteins with elusive functions,” he continued.
“We name [for example] one — PGC1-ATTrusted Source — which is a very important gene for regulation of mitochondria, our cellular powerhouses. We don’t know much about PGC1-AT and, because this new protein is highly similar in mice and humans, I think this new protein might entail very important functions which we [know] little about.”
Brown fat and obesity in humans
Humans have the most brown fat when they are babies, which helps them stay warm. The amount of brown fat in the body lowers as we age.
Adults typically have small amounts of brown fat in/around the shoulders, neck, spinal cord, kidneys, and heart.
This is not the first study to look at activating brown fat to help decrease weight and protect against obesity.
A study published in August 2019 found that activating brown fat helps to improve metabolismTrusted Source, providing potential targets for obesity and diabetes treatments.
A review of existing research, published in March 2019, reported both cold exposure and exerciseTrusted Source may help trigger brown fat in the body.
And a study published in October 2023 discovered the exact nerve pathwaysTrusted Source needed to “turn on” brown fat.
Can adults increase their brown fat levels?
If “switching on” brown fat helps to protect against obesity, can adults do anything to add more to their bodies?
Kornfeld said there is currently no consensus on that:
“In animal models, it is very clear that this decline in brown fat amount and activity can be delayed by pharmacological and environmental approaches — cold exposure [and] certain forms of drugs. As these drugs have strong side effects, many researchers are looking for more safe ways to bring back brown fat activity — e.g. in obesity and older age — or prevent its loss during the course of life.”
In an effort to increase brown fat levels in adults, current studies are looking at “browning” white fat through exercise or the use of certain drugs, such as thiazolidinediones and glucagon-like peptide-1 receptor agonists (GLP-1 agonists).
“Unfortunately, brown fat is made when you’re a fetus and as you age, you can’t really develop more brown fat,” Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA told MNT after reviewing this study. “It’s hard to grow specifically brown fat.”
“But what you can do is stimulate the brown fat cells that are still there to grow and work more,” Ali continued. “People still have stores of brown fat like their shoulders and behind the neck between their shoulder blades. So putting ice to that area or cold water baths and things can help stimulate brown fat.”
Ali said it would be great to see in humans if there’s a way to measure the amount of brown fat someone has and figure out ways to stimulate that brown fat.
“But the take-home point for most people [is that] all these things can be helpful, but if people still are not choosing or making the right food choices, then nothing is very successful,” he added. “You still have to eat the right things to lose weight.”
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https://www.medicalnewstoday.com/ar...against-obesity
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Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function
Abstract
Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5′ truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.
https://www.nature.com/articles/s42255-024-01033-8
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