Two independent studies published recently have advanced the understanding of brown adipose tissue (brown fat) and its potential role in metabolic and cardiovascular health. One study, conducted at MedUni Vienna, examined the relationship between brown fat activity and vascular inflammation in adults with obesity. A separate study, led by NYU College of Dentistry and published in Nature Communications, identified a mechanism by which the protein SLIT3 regulates brown fat activation through the expansion of its blood vessels and nerve networks.
Brown Fat and Aortic Inflammation
Study Design and Participants
A study led by Florian Kiefer at MedUni Vienna investigated the relationship between brown adipose tissue activity and vascular inflammation in 65 adults with obesity. Brown fat activity was assessed using 18F-FDG-PET/CT imaging following standardized cold exposure. Aortic inflammation was measured simultaneously.
Key Findings
Approximately one-third of participants had detectable brown fat activity. These individuals showed lower inflammatory activity in the aorta compared to participants without active brown fat. Higher brown fat activity correlated with lower levels of vascular inflammation.
Blood analyses indicated that participants with active brown fat had higher levels of anti-inflammatory and vasoprotective molecules, and lower levels of inflammation and atherosclerosis markers, compared to those without active brown fat.
Statements from Researchers
Principal investigator Florian Kiefer stated:
"In this study, we demonstrate for the first time that people with obesity who have active brown fat show less inflammation in the aortic vessel wall than comparable individuals without this tissue."
Kiefer added:
"Our findings suggest that brown fat may not only benefit metabolic health but could also act as a protective factor for the vascular system. While brown fat is primarily activated by cold exposure, research is already exploring pharmacological strategies to stimulate its activity."
Background
Brown adipose tissue is vital for heat production in newborns and infants. Its quantity and activity decline with age and are typically reduced in obesity. Unlike white fat, brown fat burns energy and contributes to heat production.
The study was conducted in collaboration with the Division of Nuclear Medicine at MedUni Vienna and the Institute of Analytical Chemistry at the University of Vienna. Further long-term studies are planned to confirm the results and investigate whether targeted activation of brown fat could reduce cardiovascular complications in people with obesity.
SLIT3 Protein and Brown Fat Activation
Brown Fat Function
Brown fat is a specialized tissue that generates heat (thermogenesis) and is linked to weight loss and metabolic health. Unlike white fat, which stores excess energy, brown fat uses resources like glucose and lipids to produce heat when activated by cold. This process consumes fuel sources, preventing them from being stored as white fat.
Brown fat relies on dense networks of nerves and blood vessels. Nerves facilitate communication with the brain for activation signals, while blood vessels supply oxygen and nutrients for heat generation and distribute heat throughout the body.
SLIT3 Mechanism
Farnaz Shamsi's lab at NYU College of Dentistry identified SLIT3, a protein secreted by brown fat cells. The study found that the enzyme BMP1 cleaves SLIT3 into two distinct fragments. These two fragments regulate different processes: one promotes the growth of blood vessels, and the other expands nerve networks. This mechanism allows for the coordinated regulation of both essential components.
Further research identified the PLXNA1 receptor, which binds to one of the SLIT3 fragments to control brown fat's nerve network. Studies in mice demonstrated that removing SLIT3 or the PLXNA1 receptor impaired brown fat's nerve structure and blood vessel density, leading to cold sensitivity and difficulty maintaining body temperature.
Human Relevance
An examination of fat tissue samples from over 15,000 individuals, including those with obesity, indicated that SLIT3 gene expression may regulate fat tissue health, inflammation, and insulin sensitivity in humans.
Therapeutic Potential
While many weight loss drugs, such as GLP-1s, primarily suppress appetite, treatments involving brown fat have the potential to increase energy expenditure. The detailed understanding of SLIT3's role in controlling brown fat's infrastructure highlights several processes that could be targeted for therapeutic interventions to improve brown fat's heat production capacity and metabolic benefits.
The discovery was published in Nature Communications.