Until recently, our body fat, the adipose organ, was thought to be composed by white adipose tissue, which has been described merely as a passive storage organ for excess calories, and of brown adipose tissue, described to be present in infants, which functions primarily to consume fat to produce heat to maintain core body temperature.

However, our understanding of the composition and the importance of the adipose organ has been revised since brown fat was discovered to play a role in adult humans and a whole new shade of beige fat was identified. To tackle obesity and its related health risks, we need to understand how these three types of fat function.

White adipose tissue’s role in buffering nutrient availability and demand by storing excess calories and preventing their toxic accumulation in non-adipose tissues such as liver and muscle has been widely described and investigated. We also understand its importance in secreting cell-signalling proteins called adipokines as part of a dynamic endocrine system that regulates nutrient partitioning into peripheral organs.

Like white adipocytes, brown adipocytes accumulate and store lipids. However, brown adipocytes have more abundant mitochondria, enriched with uncoupling protein 1 (UCP1), which produces heat following exposure to thermogenic stimuli such as cold and the consumption of foods that are heavily enriched in fat content. According to our observations in rodents, heat production by brown adipose tissue is an extremely energy-expensive process that burns nutrients and when stimulated has an enormous impact on energy balance, metabolism and body weight regulation.

The revelation that adult humans possess such a potent metabolic tissue has been recently accompanied by the discovery that UCP1-expressing thermogenic adipocytes can also been found in white adipose tissue depots in the form of beige (brite) adipocytes. In rodents, these newly described adipocytes respond to the same stimuli that drive brown adipose tissue activation, such as chronic cold exposure, and they also contribute to heat production. As part of the same response, these beige cells are recruited in white adipose tissue, resulting in its browning.

Also, while there is a significant overlap between beige and brown adipocytes in terms of UCP1 expression and genes required to activate thermogenesis, beige adipocyte possess a distinctive gene expression profile compared to brown cells, indicating that they are distinct types of thermogenic cells.

In summary, when considering adipose tissue involvement in the regulation of energy balance, the contribution of the three different “shades” of fat — white, brown and beige — should be taken into account. Furthermore, the discovery of these different shades of fat has important implications if we consider the mechanisms underlying obesity-related metabolic complications and the treatment of these conditions.

White adipose tissue dysfunction contributes to the metabolic syndrome, a combination of obesity, diabetes and increased risk of cardiovascular disease. This is because individuals have a functional limit beyond which white adipose tissue fails to function as a storage and an endocrine organ, resulting in toxic accumulation of lipids in other organs, such as the liver and muscle.
Conceptually, this lipotoxic effect could be ameliorated either by increasing the capacity of white adipose to expand and store nutrients and/or by eliminating excess calories by increasing the activity and capacity of brown and/or beige cells to burn them.

In our opinion, the development of a successful adipose-tissue based therapeutic strategy to treat obesity and related metabolic complications is reliant on a good understanding of basic adipose-tissue biology.

In our review, we discuss in more detail how rodent models have deepened our understanding of the developmental origins and cell-type specific regulators on white, brown and beige adipocytes and also the current challenge of translating this information from rodents to humans.

Stefania Carobbio is a postdoctoral research associate at the Wellcome Trust Sanger Institute and the University of Cambridge Metabolic Research Laboratories. She works in Toni Vidal-Puig’s group, which investigates molecular mechanisms that control energy expenditure and brown fat activation.

References

• Peirce, V et al (2014). The different shades of fat. Nature. doi:10.1038/nature13477

Post originally published at the Sanger Blog in July 2014: https://sangerinstitute.wordpress.com/2014/07/02/three-shades-of-fat/