Assembling the adipose organ: adipocyte lineage segregation and adipogenesis in vivo

Abstract

Adipose tissue is composed of anatomically distinct depots that mediate several important aspects of energy homeostasis. The past two decades have witnessed increased research effort to elucidate the ontogenetic basis of adipose form and function. In this Review, we discuss advances in our understanding of adipose tissue development with particular emphasis on the embryonic patterning of depot-specific adipocyte lineages and adipocyte differentiation in vivo Micro-environmental cues and other factors that influence cell identity and cell behavior at various junctures in the adipocyte lineage hierarchy are also considered.

Keywords: Adipocyte; Adipocyte lineages; Adipocyte precursors; Adipogenesis; Adipose; Adipose stem cells.

Fig. 1.

Adipose tissue publication metrics. (A) Adipose tissue has received little research attention compared with other organs/tissues, as illustrated by a bar graph depicting the number of published papers focusing on specific organs/tissues. To construct the graph, each organ/tissue name was typed into the search box on PubMed in January 2019, and the number of items returned for each organ/tissue was plotted. (B) Research investment in adipose has grown, yet is biased toward studies on adipose metabolism. As for the graph in A, the terms ‘adipose’, ‘adipose metabolism’ or ‘adipose development’ were typed into the search box on PubMed. Results by year are shown. Major discoveries in adipose development are also noted along the timeline. The original derivation of 3T3-L1 cells has been described previously (Green and Meuth, 1974). Other major discoveries along the timeline are referred to in the main text.

Fig. 2.

Anatomical distribution of brown and white fat depots in the mouse. Brown fat depots are shown in brown and white fat depots are shown in pink. The visceral cavity is indicated by a dotted line. Notably, the anterior subcutaneous white adipose depot (asWAT) appears to be continuous with the interscapular white adipose depot (inscWAT) under obese conditions. The inscWAT and asWAT overlie the more internal interscapular and subscapular brown depots (inscBAT and subscBAT, respectively). cBAT, cervical brown adipose tissue; ingWAT, inguinal white adipose tissue; mWAT, mesenteric white adipose tissue; paBAT, peri-aortal brown adipose tissue; pgWAT, perigonadal white adipose tissue; prBAT, perirenal brown adipose tissue; rWAT, retroperitoneal white adipose tissue; savWAT, salivary gland white adipose tissue.

Fig. 3.

Embryonic patterning of adipocyte lineages. (A) Schematic of an ∼E9.5 mouse embryo. Cross-sectional views show relevant mesodermal and neuro-ectodermal subcompartments. (B) A model adipocyte lineage tree. This tree was constructed based on current lineage-tracing data in mice. Beige adipocytes are not included in the tree, given that it is unclear whether these cells are specified embryonically. *The triceps white adipose depot (triWAT) is not a subcutaneous adipose depot. Rather, it is an internal supra-muscular depot. Grey text indicates specific adipose depots; arrows indicate cell lineage progression; '?' indicates an unknown in the field. inscBAT and inscWAT are outlined as <50% of adipocytes in these depots are derived from progenitors of the central dermomyotome. asWAT, anterior subcutaneous white adipose tissue; inscBAT, interscapular brown adipose tissue; inscWAT, interscapular white adipose tissue; PLPM, posterior lateral plate mesoderm.

Fig. 4.

Adipocyte hyperplasia is regulated by dietary, micro-environmental and hormonal cues. New adipocytes form through the proliferation and differentiation of depot-resident adipocyte precursor cells. This process is combinatorially regulated in vivo. However, the molecular mechanisms by which different cues influence adipocyte hyperplasia are only beginning to be understood.