Developmental Origins of the Adipocyte Lineage: New Insights from Genetics and Genomics Studies

Abstract

The current epidemic of obesity and overweight has caused a surge of interest in the study of adipose tissue formation. Much progress has been made in defining the transcriptional networks controlling the terminal differentiation of adipocyte progenitors into mature adipocytes. However, the early steps of adipocyte development and the embryonic origin of this lineage have been largely disregarded until recently. In mammals, two functionally different types of adipose tissues coexist, which are both involved in energy balance but assume opposite functions. White adipose tissue (WAT) stores energy, while brown adipose tissue (BAT) is specialized in energy expenditure. WAT and BAT can be found as several depots located in various sites of the body. Individual fat depots exhibit different timing of appearance during development, as well as distinct functional properties, suggesting possible differences in their developmental origin. This hypothesis has recently been revisited through large-scale genomics studies and in vivo lineage tracing approaches, which are reviewed in this report. These studies have provided novel fundamental insights into adipocyte biology, pointing out distinct developmental origins for WAT and BAT, as well as for individual WAT depots. They suggest that the adipose tissue is composed of distinct mini-organs, exhibiting developmental and functional differences, as well as variable contribution to obesity-related metabolic diseases.

Epigenetics and developmental programming of welfare and production traits in farm animals

“…Although brown fat has been predominantly associated with young animals (e.g. newborn lambs), BAT deposits have also been identified in adult animals (Billon and Dani 2012). This division into WAT and BAT has been questioned recently, and animals raised in cold conditions also have extensive brownlike adipocytes in their WAT fat depots, with such cells now referred to as either BRITE or beige adipose cells (Wu et al 2012) It is unclear whether these cells are white cells that have changed their phenotype or whether they are brown cells that form in the WAT from a separate stem cell population or a mixture of both (Liu et al 2013).…”

Adipose tissue dysregulation and metabolic consequences in childhood and adolescent obesity: potential impact of dietary fat quality

“…Early in this process, mesenchymal precursor cells differentiate into preadipocytes (123) after which intense preadipocyte proliferation continues until approximately 23 weeks gestation (122) . By week 28, WAT is present in the principal fat depots throughout the body (123) , while brown adipose tissue (BAT) can be identified earlier in development (124) . At full term, AT accounts for approximately 20 % of body mass in infants born an appropriate weight for gestational age (AGA); 80-90 % of which is stored subcutaneously (125)(126)(127)(128) .…”

Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways

“…The identification of a consistent and rather uniform pattern of differentially expressed genes between the two fat depots using multiple array replicates opened new perspectives for future research on regional differences in adipose tissue biology (377). A recent review summarizes results from genetic and genomic studies that led to major insights in the developmental origin of adipocyte lineage (22).…”