Fifty shades of white: Understanding heterogeneity in white adipose stem cells

Abstract

The excessive expansion of white adipose tissue underlies the global obesity epidemic. However, not all fat is equal, and the impact of heterogeneity on the development and expansion of different adipose depots is becoming increasingly apparent. Two mechanisms are responsible for the growth of adipose tissue: hyperplasia (increasing adipocyte number) and hypertrophy (increasing adipocyte size). The former relies on the differentiation of adipocyte stem cells, which reside within the adipose stromal vascular fraction. Many differences in gene expression, adipogenesis, and the response to obesogenic stimuli have been described when comparing adipose stem cells from different depots. Considering that there is disparity in the pathogenicity of the depots, understanding this heterogeneity has clinically relevant implications. Here we review the current knowledge surrounding such differences, in the context of development, expansion and therapeutics. Moreover, given the importance of these differences, we suggest that careful consideration for the precise methodologies used, is essential if we are to truly understand the physiologically relevant consequences of this heterogeneity.

Dysregulated lipid storage and its relationship with insulin resistance and cardiovascular risk factors in non-obese Asian patients with type 2 diabetes

“…These cells respond to surplus energy through processes of proliferation or expansion so called adipocyte hyperplasia or adipocyte hypertrophy, respectively. Preadipocytes of subcutaneous adipose tissue replicate and differentiate into mature adipocytes (adipocyte hyperplasia) more efficiently than those of visceral depot [25]. The mature adipocyte has its maximum capacity for expansion which is determined by genetic, gender or certain hormones [25][26][27].…”

“…Preadipocytes of subcutaneous adipose tissue replicate and differentiate into mature adipocytes (adipocyte hyperplasia) more efficiently than those of visceral depot [25]. The mature adipocyte has its maximum capacity for expansion which is determined by genetic, gender or certain hormones [25][26][27]. The study by Sato et al [28] in non-diabetic Japanese adults indicates that the maximum storage capacity of abdominal subcutaneous fat occurs at BMI of 23-24 kg/m 2 in women and 24-25 kg/m 2 in men.…”

Bioactivity and composition of a preserved connective tissue matrix derived from human placental tissue

“…Previous research has shown that there exists a good deal of heterogeneity between ASCs derived from different individuals and even from different regions within the same individual. 31,32 Overall though, these results indicate that the FPTM does not have a negative effect on ASC gene expression and cell behavior in vitro.…”

Oligomers of the lipodystrophy protein seipin may co-ordinate GPAT3 and AGPAT2 enzymes to facilitate adipocyte differentiation

“…However, while all WAT depots are absent in seipin-deficient CGL patients, including those spared in AGPAT2 deficiency, seipin appears dispensable for BAT development, at least in mice 7,30,31 . Thus, it is increasingly apparent that the pathways governing the development and expansion of adipose mass differs significantly between depots depending on location and the identity of the stem cells involved 32,33 . Such complexity is also likely to apply when considering the roles of different GPAT isoforms in these processes.…”