Vitamin A and cold temperatures could lead to novel obesity therapeutics: study

A new study from MedUni Vienna's Division of Endocrinology and Metabolism found that cold temperatures increase vitamin A levels in humans and mice. The process stimulates heat generation and fat burning by converting white fat into brown fat. 

Unlike white fat, brown fat burns calories through fatty acid oxidation and heat production. As obesity develops, excess calories are mostly stored in white fat while brown fat burns energy and generates heat. Over 90% of body fat in humans is white and typically located in the midsection. 

The biggest activator of brown fat is moderate cold exposure, according to the researchers. The findings further bolster the fat conversion as a promising target for novel obesity therapeutics. 

Cold temperatures burn fat 

This new research piggybacks off a previous study​ from April, which found that short-term cold exposure may help people with brown fat burn 15% more calories than those without. The small study, led by Florian W. Kiefer, M.D., Ph.D., of the Medical University of Vienna in Austria, was published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism​.

"This data improves our understanding of how brown fat works in humans," ​said Kiefer. "We found that individuals with active brown fat burned 20 more kilocalories than those without."​

Current research 

Now, Kiefer is further demonstrating that moderate application of cold increases the levels of vitamin A and its blood transporter, retinol-binding protein, in both humans and mice in newer research published in the journal Molecular Metabolism​.

The new study explained that most of the vitamin A reserves are stored in the liver, and cold exposure appears to stimulate the redistribution of vitamin A toward the fat. The cold-induced increase in vitamin A led to a conversion of white fat into brown fat, with a higher rate of fat burning.

While the researchers found the transformation of white fat into brown fat reduces obesity in many preclinical models, they acknowledge that the physiologic importance of systemic retinoid transport for brown fat and adaptive thermogenesis is unknown.

Key findings 

The research team performed cold exposure studies in mice and humans. The researchers blocked the vitamin A transporter retinol-binding protein in mice by genetically manipulating the mice. This led to both the cold-mediated rise in vitamin A and the browning of the white fat to be halted. "As a consequence, fat oxidation and heat production were perturbed so that the mice were no longer able to protect themselves against the cold,"​ explained Kiefer. In contrast, the addition of vitamin A to human white fat cells led to the expression of brown fat cell characteristics, with increased metabolic activity and energy consumption.

Keifer said that the results show that vitamin A plays an important role in the function of fat and affects global energy metabolism -- but don’t stock up on vitamin A just yet. “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," ​cautioned Keifer. "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."​

Source: Molecular Metabolism​

2020, 101088 doi.org/10.1016/j.molmet.2020.101088​

“Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis”​

Authors: A. Fenzyl et al.