Metabolic interplay between white, beige, brown adipocytes and the liver

Abstract

In mammalian evolution, three types of adipocytes have developed, white, brown and beige adipocytes. White adipocytes are the major constituents of white adipose tissue (WAT), the predominant store for energy-dense triglycerides in the body that are released as fatty acids during catabolic conditions. The less abundant brown adipocytes, the defining parenchymal cells of brown adipose tissue (BAT), internalize triglycerides that are stored intracellularly in multilocular lipid droplets. Beige adipocytes (also known as brite or inducible brown adipocytes) are functionally very similar to brown adipocytes and emerge in specific WAT depots in response to various stimuli including sustained cold exposure. The activation of brown and beige adipocytes (together referred to as thermogenic adipocytes) causes both the hydrolysis of stored triglycerides as well as the uptake of lipids and glucose from the circulation. Together, these fuels are combusted for heat production to maintain body temperature in mammals including adult humans. Given that heating by brown and beige adipocytes is a very-well controlled and energy-demanding process which entails pronounced shifts in energy fluxes, it is not surprising that an intensive interplay exists between the various adipocyte types and parenchymal liver cells, and that this influences systemic metabolic fluxes and endocrine networks. In this review we will emphasize the role of hepatic factors that regulate the metabolic activity of white and thermogenic adipocytes. In addition, we will discuss the relevance of lipids and hormones that are secreted by white, brown and beige adipocytes regulating liver metabolism in order to maintain systemic energy metabolism in health and disease.

Keywords: Adipokines; Bile acids; Brown adipose tissue; Hepatokines; Lipid metabolism; Lipokines; Lipoproteins; Metabolic disease; Non-alcoholic fatty liver disease; Triglycerides; White adipose tissue.