The Common and Distinct Features of Brown and Beige Adipocytes

Abstract

Two types of thermogenic fat cells, brown adipocytes and beige adipocytes, play a key role in the regulation of systemic energy homeostasis in mammals. Both brown fat and beige fat possess thermogenic properties in addition to common morphological and biochemical characteristics, including multilocular lipid droplets and cristae-dense mitochondria. Recent studies also identify features that are distinct between the two types of thermogenic fat cells, such as their developmental regulation and function. Of particular interest is the role of beige fat in the regulation of glucose homeostasis via uncoupling protein 1 (UCP1)-independent mechanisms. A better understanding of the underlying causes of these characteristics of brown and beige fat will allow us to specifically manipulate these cells to improve systemic energy metabolism and glucose homeostasis.

Keywords: UCP1; beige adipocytes; brown adipocytes; diabetes; obesity.

Figure 1. Anatomical locations of thermogenic fat in mice and humans

Classical brown adipocytes reside in dedicated BAT depots, including interscapular, axillary, and perirenal BAT depots in mice and infants. Beige adipocytes sporadically reside in subcutaneous WAT depots, such as the inguinal and anterior subcutaneous WAT in mice (arrowheads indicate the multilocular beige adipocytes). In adult humans, BAT exist in multiple locations, such as cervical, supraclaviscular, axillary, paravertebral, and abdominal subcutaneous regions. UCP1-positive adipocytes from the supraclavicular region show a molecular signature resembling mouse beige adipocytes, whereas the deep neck regions contain thermogenic fat that resembles classical brown adipocytes in mice.

Figure 2. Developmental lineages of thermogenic adipocytes

Classical brown adipocytes differentiate during embryonic development from a subset of dermomytomal precursors that express En1, Myf5, and Pax7. Development of beige adipocytes in subcutaneous WAT depots is stimulated by enviornmental, such as chronic cold acclimation, exercise, PPARg ligands, tissue injury, and cancer cachexia. When the external stimuli are withdrawn, the recruited beige adipocytes directly acquire a white fat phenotype with unilocular lipid droplets and no UCP1 expression.

Figure 3. Anti-obesity and anti-diabetic actions of beige fat are UCP1-independent

Adipose tissue-selective PRDM16 transgenic (Prdm16 Tg) mice are protected from diet-induced obesity and glucose intolerance (see phenotypes on the right). When crossed in Ucp1−/− background, many of the metabolic phenotypes in wild-type background are preserved in Prdm16 Tg x Ucp1−/− mice [63].