11.03.20
A recent preclinical study published in the journal Molecular Metabolism provided evidence that cold ambient temperatures increase concentrations of vitamin A in both humans and mice, which stimulates the conversion of white adipose tissue into brown adipose tissue – which stimulates fat burning and heat generation, the authors report. The study was authored by a research group at the Medical University of Vienna’s Division of Endocrinology and Metabolism, with involvement from scientists from Harvard University, Boston, and Rutgers University in New Jersey.
White and brown adipose tissues are the two types of fatty depots present in mammals, and previous research has shown that excess calories are mainly stored in white fat during the development of obesity, while, in contrast, brown fat burns energy and thereby generates heat. White fat depots comprise approximately 90% of total body fat stores in humans.
The hypothesis for the clinical trial hinged on thermogenesis, an adaptive biologic function required for mammals to survive. During this process, white adipose tissue is known to take on the characteristics of the more energy-wasting brown adipose tissue, which results in a quicker burning of calories.
“We are aware that retinoid plasma concentrations per se may not necessarily have a dramatic biological impact,” the authors said. “However it has been demonstrated that very subtle changes in the tissue retinoid content can have substantial functional effects, particularly on the transcriptional level. It is also possible that longer cold challenges may have even more pronounced effects on retinoid metabolism and biological outcomes, such as white adipose tissue browning.”
In both humans and mice, exposure to cold temperatures increases levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most vitamin A reserves are stored in the liver, and cold exposure seems to stimulate the redistribution of vitamin A toward the adipose tissue, the authors wrote. This led to a conversion of white fat to brown fat, with a higher rate of fat burning.
This was determined through cold exposure studies on humans and mice. Thirty healthy, lean subjects were exposed to moderate cold, 14-17 degrees Celsius, which caused their circulating retinol and retinol-binding proteins to increase after 2.5 hours. The phenomenon was also observed in mice exposed to 4 degrees Celsius for 24 hours.
The researchers blocked the vitamin A transporter “retinol-binding protein” in mice, via genetic manipulation. This blunted both the cold-induced rise in vitamin A and the browning of the white fat seen in the absence of genetic manipulation.
“As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold,” Florian Kiefer, the lead author of the study, said. “Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time. We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism.
White and brown adipose tissues are the two types of fatty depots present in mammals, and previous research has shown that excess calories are mainly stored in white fat during the development of obesity, while, in contrast, brown fat burns energy and thereby generates heat. White fat depots comprise approximately 90% of total body fat stores in humans.
The hypothesis for the clinical trial hinged on thermogenesis, an adaptive biologic function required for mammals to survive. During this process, white adipose tissue is known to take on the characteristics of the more energy-wasting brown adipose tissue, which results in a quicker burning of calories.
“We are aware that retinoid plasma concentrations per se may not necessarily have a dramatic biological impact,” the authors said. “However it has been demonstrated that very subtle changes in the tissue retinoid content can have substantial functional effects, particularly on the transcriptional level. It is also possible that longer cold challenges may have even more pronounced effects on retinoid metabolism and biological outcomes, such as white adipose tissue browning.”
In both humans and mice, exposure to cold temperatures increases levels of vitamin A and its blood transporter, retinol-binding protein, in humans and mice. Most vitamin A reserves are stored in the liver, and cold exposure seems to stimulate the redistribution of vitamin A toward the adipose tissue, the authors wrote. This led to a conversion of white fat to brown fat, with a higher rate of fat burning.
This was determined through cold exposure studies on humans and mice. Thirty healthy, lean subjects were exposed to moderate cold, 14-17 degrees Celsius, which caused their circulating retinol and retinol-binding proteins to increase after 2.5 hours. The phenomenon was also observed in mice exposed to 4 degrees Celsius for 24 hours.
The researchers blocked the vitamin A transporter “retinol-binding protein” in mice, via genetic manipulation. This blunted both the cold-induced rise in vitamin A and the browning of the white fat seen in the absence of genetic manipulation.
“As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold,” Florian Kiefer, the lead author of the study, said. “Our results show that vitamin A plays an important role in the function of adipose tissue and affects global energy metabolism. However, this is not an argument for consuming large amounts of vitamin A supplements if not prescribed, because it is critical that vitamin A is transported to the right cells at the right time. We have discovered a new mechanism by which vitamin A regulates lipid combustion and heat generation in cold conditions. This could help us to develop new therapeutic interventions that exploit this specific mechanism.
