Deciphering White Adipose Tissue Heterogeneity

Abstract

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.

Keywords: adipose tissue; development; metabolic syndrome; obesity.

Figure 1

Comparison between Human and Rodent Adipose Tissues. White Adipose Tissues (WAT) are mostly visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Major visceral depots common in both humans and rodents include epicardial/pericardial (not shown), perirenal (prWAT), retroperitoneal (rWAT), and mesenteric WAT (mWAT). While humans have large omental (oWAT) fat, mice have large perigonadal (pgWAT) fat. SAT in humans can be divided into upper (abdominal) and lower (gluteofemoral). Abdominal fat in human can be further divided into superficial and deep, which are separated anatomically by Scarpa’s Fascia. In mice, SAT is divided into anterior and posterior. Dermal WAT (dWAT) is another fat depot that exists in both humans and mice. dWAT is located in the dermis and above the SAT (note: this separation is visible by the presence of striated muscular layer known as panniculus carnosus only found in mice). Bone marrow adipose tissue (BMAT or MAT) is also another adipose depot common in both species. Cephalad and caudad are also referred to as anterior and posterior in mice, respectively.

Figure 2

Heterogeneous Origins of White Adipose Tissue Depots. Adipose precursor cells of individual adipose depots originate from distinct areas of mesoderm. While Meox1/Pax3/Pax7- (from paraxial mesoderm) derived adipocytes predominate in the dorsoanterior depots, HoxB6- (lateral plate mesoderm) derived adipocytes are found largely in the ventral regions. Like Meox1/Pax3/Pax7 derived adipocytes, Mx1 and Myf5 derived adipocytes are also found in dorsoanterior depots. Adipocytes derived from the Prx1 lineage are found only subcutaneous depots, while adipocytes derived from the mesothelium and marked by Wt1 expression are only found in the visceral depots. Adipocytes derived from the Tagln lineage are found in all adipose tissue depots. Dotted lines indicate a potential connection among these lineages.