Tag: brown fat

Categories : Dermatology Diet and NutritionTags :

UV Exposure Increases Appetite but Suppresses Weight Gain

On By ModernMedia
Photo by Julian Jagtenberg on Pexels

In a novel study, a team of dermatologists evaluated the effect of ultraviolet (UV) exposure on appetite and weight regulation. They found that UV exposure raises norepinephrine levels, decreases leptin levels, and induces the browning of subcutaneous fat, thereby increasing energy expenditure. These results potentially pave the way for new approaches to prevent and treat obesity and metabolic disorders. Their findings appear in the Journal of Investigative Dermatology, published by Elsevier.

Co-first authors Qing-Ling Quan, MD, PhD, and Eun Ju Kim, PhD, Department of Dermatology, Seoul National University Hospital, explained, “Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. Subcutaneous fat is a critical organ in regulating energy homeostasis. Alongside previous studies on the effects of UV exposure on obesity and metabolic disorders, our team was inspired by our prior discovery that, although UV rays do not directly reach subcutaneous fat when exposed to the skin, they can regulate the metabolism of subcutaneous fat. This led us to hypothesise that skin exposure to UV rays could play a significant role in systemic energy homeostasis, prompting this research.”

Investigators discovered that when exposed to UV radiation consistently, mice fed a normal diet and those on a high-fat diet exhibited increased appetite due to a decrease in leptin, a key hormone in appetite regulation. But there was no weight increase – they found that UV radiation inhibits weight gain by enhancing secretion of the neurotransmitter norepinephrine, which not only decreases leptin but also increases energy expenditure through the “browning” of subcutaneous fat.

The increased energy intake, driven by heightened appetite, is converted to heat and burned before it can accumulate in subcutaneous fat, thus preventing weight gain.

This research provides new insights into the impact of UV exposure on appetite and weight regulation, opening possibilities for novel approaches in the prevention and treatment of obesity and metabolic disorders. Specifically, uncovering the mechanism by which UV radiation prevents weight gain could offer new approaches to dietary regulation and weight loss, providing innovative insights into health and obesity management that could positively impact human health.

Lead investigator Jin Ho Chung, MD, PhD, Department of Dermatology, Seoul National University Hospital, Seoul National University College of Medicine, explained, “This study elucidates the mechanism by which UV exposure can increase appetite while inhibiting weight gain. These findings contribute significantly to understanding the effects of UV radiation on energy metabolism and homeostasis and open new avenues for exploring prevention and treatment strategies for obesity and metabolic disorders. Notably, the fact that UV radiation lowers leptin levels and increases norepinephrine, thereby promoting the browning of subcutaneous fat and increasing energy expenditure, provides a groundbreaking clue for the development of obesity treatment strategies. This research demonstrates that UV exposure not only affects the skin but also plays a deep role in our body’s energy metabolism and homeostasis processes. However, further research is needed on the long-term effects and safety of UV exposure, and there should be significant interest in developing new therapeutic approaches that utilise the efficacy of UV radiation.”

However, as co-corresponding author Dong Hun Lee, MD, PhD, Institute of Human-Environment Interface Biology, Seoul National University, noted, “Because UV exposure can accelerate skin aging and promote skin cancer, it is advisable to minimise UV exposure and protect the skin with sunscreen. Thus, our research team plans to conduct follow-up studies to develop new strategies that could mimic the effects of UV radiation for obesity and metabolic regulation.”

Source: Elsevier

Categories : COVIDTags :

How to Prevent Dangerous Weight Loss in COVID Patients

On By ModernMedia
Photo by Stephen Andrews on Unsplash

COVID infection often causes adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process with an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID associated weight loss by targeting the blood vessels in the fat tissues,” says corresponding author Yihai Cao, professor at Karolinska Institutet.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Similar mechanisms in humans

The researchers observed the same mechanisms in human tissue samples from four patients who died of COVID, suggesting the findings could be clinically relevant for humans.

When the animals were treated with an anti-VEGF drug, the animals recovered most of their lost weight and their fat tissues exhibited fewer microvessels.

“Antiangiogenic drugs are currently used in the clinic to treat various types of cancers,” Yihai Cao says. “It’s possible these drugs could also be helpful in treating COVID-related problems such as excessive weight loss and metabolic changes, thus improving the quality of life and survival for these patients. Of course, we will need more research to validate if our preclinical findings also hold up in human trials.”

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Metabolite Discovery Could Turn ‘Bad’ Fat to ‘Good’ Fat

On By ModernMedia
Obesity
Image source: Pixabay CC0

Metabolites are the substances made and used during the body’s metabolic processes – or, as a new discovery out of Scripps Research and its drug development arm, Calibr, indicates, they could also be potent molecules for treating severe diseases.

In a study published in the journal Metabolites, the researchers used novel drug discovery technologies to uncover a metabolite that converts white adipocytes (‘bad’ fat cells) to brown adipocytes (‘good’ fat cells). This discovery suggests a pathway to treating metabolic disorders such as obesity, type 2 diabetes and cardiovascular disease. This creative drug discovery method could also identify countless other potential therapeutics.

“The reason many types of molecules don’t go to market is because of toxicity,” said co-senior author Gary Siuzdak, PhD. “With our technology, we can pull out endogenous metabolites – meaning the ones that the body makes on its own – that can have the same impact as a drug with less side effects. The potential of this approach is even evidenced by the FDA’s recent approval of Relyvrio, the combination of two endogenous metabolites for the treatment of amyotrophic lateral sclerosis (ALS).”

Metabolic diseases are often caused by an imbalance in energy homeostasis. This is why certain therapeutic approaches have centred around converting white adipocytes into brown adipocytes. White adipocytes store excess energy and can eventually result in metabolic diseases like obesity, while brown adipocytes dissolve this stored energy into heat – ultimately increasing the body’s energy expenditure and helping bring balance.

To uncover a therapy that could stimulate the production of brown adipocytes, the researchers searched through Calibr’s ReFRAME drug-repurposing collection – a library of 14 000 known drug compounds that have been approved by the FDA for other diseases or have been extensively tested for human safety. Using high-throughput screening – an automated drug discovery method for searching through large pools of information –the scientists scanned ReFRAME for a drug with these specific capabilities.  

This is how they uncovered zafirlukast, an FDA-approved drug used for treating asthma. Through a set of cell culture experiments, they found zafirlukast could turn adipocyte precursor cells (known as preadipocytes) into predominantly brown adipocytes, as well as convert white adipocytes into brown adipocytes.

Unfortunately, zafirlukast is toxic at higher doses, and it wasn’t entirely clear how zafirlukast was converting the adipocytes. This is when the researchers partnered with Dr Siuzdak and his team of metabolite experts.

“We needed to use additional tools to break down the chemicals in zafirlukast’s mechanism,” explained Kristen Johnson, PhD, co-senior author of the paper. “Framed another way, could we find a metabolite that was providing the same functional effect that zafirlukast was, but without the side effects?”

Dr Siuzdak and his team designed a novel set of experiments, known as drug-initiated activity metabolomics (DIAM) screening, to help answer Johnson’s question. DIAM uses technologies such as liquid chromatography (a tool that separates components in a mixture) and mass spectrometry (an analytical technique that separates particles by weight and charge) to pool through thousands of molecules and identify specific metabolites. In this case, the researchers were searching through adipose tissue for metabolites that could lead to brown adipocyte cell production.

After reducing 30 000 metabolic features to just 17 metabolites, they came upon myristoylglycine – an endogenous metabolite that prompted the creation of brown adipocytes, without harming the cell. Of the thousands of metabolic features measured in the analysis, only myristoylglycine had this special characteristic, even among nearly structurally identical metabolites.

“Identifying myristoylglycine among the thousands of other molecules speaks to the power of Siuzdak’s approach and these technologies,” added Dr Johnson. “Our findings illustrate what happens when an analytical chemistry team and a drug discovery group closely collaborate with each other.”

Source: Scripps Research

Categories : Metabolic DisordersTags :

Cold Temperatures Could Reduce Obesity-induced Inflammation

On By ModernMedia
Photo by Ian Keefe on Unsplash

In a new paper published in Nature Metabolism, researchers found that cold temperature exposure resolved obesity-induced inflammation while improving insulin sensitivity and glucose tolerance in diet-induced obese mice. The process depended on brown adipose tissue producing a molecule called Maresin 2 when stimulated by cold.

Brown adipose tissue is known to be an active endocrine orgain which helps dissipate stored energy and might promote weight loss and metabolic health.  

“Extensive evidence indicates that obesity and metabolic syndrome are linked with chronic inflammation that leads to systemic insulin resistance, so interrupting inflammation in obesity could offer promising therapies for obesity-related disease,” said co-corresponding author Yu-Hua Tseng, PhD, professor of medicine at Harvard Medical School.  “We discovered that cold exposure reduced inflammation and improved metabolism in obesity, mediated at least in part by the activation of brown adipose tissue. These findings suggest a previously unrecognized function of brown adipose tissue in promoting the resolution of inflammation in obesity.”

In two previous studies, Tseng and colleagues discovered that cold exposure could activate brown fat to produce specific lipid mediators that regulate nutrient metabolism. In the current study, the researchers identified a novel role for a lipid mediator produced from brown fat to resolve inflammation.

In the present study, the scientists created a mouse model that becomes obese when fed a typical high-fat, Western diet. When the animals were exposed to a cold environment (around 4°C), the researchers observed that the animals’ insulin sensitivity and glucose metabolism improved and their body weight decreased, compared to control animals maintained at a thermoneutral zone – the environmental temperature where the body does not need to produce heat for maintaining its core body temperature. What’s more, the scientists also noticed a profound improvement in inflammation, as measured by reduced levels of a major inflammatory marker. 

“We found that brown fat produces Maresin 2, which resolves inflammation systemically and in the liver,” said co-corresponding author Matthew Spite, PhD, a lead investigator at Brigham and Women’s Hospital and Associate Professor of Anesthesia at Harvard Medical School. “These findings suggest a previously unrecognized function of brown adipose tissue in promoting the resolution of inflammation in obesity via the production of this important lipid mediator.”

Moreover, these findings also suggest that Maresin 2 could have clinical applications as a therapy for patients with obesity, metabolic disease, or other diseases linked to chronic inflammation; however, the molecule itself breaks down quickly in the body. Tseng and colleagues seek a more stable chemical analog for clinical use.

The team notes a shortcut to improved metabolic health may already exist. Multiple human studies show that exposure to mild cold temperatures (10 to 13°C) have been shown to be sufficient to activate brown adipose tissue and improve metabolism, though the mechanisms are not well understood.

Source: EurekaAlert

Categories : Environmental EffectsTags :

Obesity Connection to Commonly-used Pesticide

On By ModernMedia
Photo by Arjun MJ on Unsplash

A commonly-used pesticide could be contributing to the global obesity epidemic, according to a new study.

Researchers discovered that chlorpyrifos slows down the burning of calories in the brown adipose tissue of mice. Reducing this burning of calories, a process known as diet-induced thermogenesis, causes the body to store these extra calories, promoting obesity. Chlorpyrifos is banned for use on foods in Canada, and also now banned in the US and, as of last year, the EU, but widely sprayed on fruits and vegetables in many other parts of the world. In South Africa it is banned for residential use but is still used in agriculture.

Scientists made the discovery after studying 34 commonly used pesticides and herbicides in brown fat cells and testing the effects of chlorpyrifos in mice fed high calorie diets. Their findings were published in Nature Communications and could have important implications for public health.

“Brown fat is the metabolic furnace in our body, burning calories, unlike normal fat that is used to store them. This generates heat and prevents calories from being deposited on our bodies as normal white fat. We know brown fat is activated during cold and when we eat,” said senior author Gregory Steinberg, professor of medicine and co-director of the Centre for Metabolism, Obesity, and Diabetes Research at McMaster.

“Lifestyle changes around diet and exercise rarely lead to sustained weight loss. We think part of the problem may be this intrinsic dialling back of the metabolic furnace by chlorpyrifos.”

Steinberg said chlorpyrifos would only need to inhibit energy use in brown fat by 40 calories every day to trigger obesity in adults, which would translate to an extra 2kg of weight gain per year.

He said that while several environmental toxins including chlorpyrifos have been associated with increasing obesity rates in both humans and animals, these studies have mostly attributed weight gain to increases in food intake and not calorie burning.

“Although the findings have yet to be confirmed in humans, an important consideration, is that whenever possible consume fruits and vegetables from local Canadian sources and if consuming imported produce, make sure it is thoroughly washed,” said Steinberg.

Source: Medical Xpress