Sorting out adipocyte precursors and their role in physiology and disease

Abstract

The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice. With new tools available, the properties of adipocyte precursors can now be defined, and the regulation and function of adipose plasticity in development and physiology can be explored.

Keywords: adipocyte precursor; adipogenesis; beige adipocytes; brown adipocytes; white adipocytes.

Figure 1.

Adipocyte precursor heterogeneity in mice. (A) Characterized fetal adipose precursor populations: Three adipose progenitor populations have been characterized in the developing inguinal WAT depot. The degree of overlap in these populations is unclear. Seale and colleagues (Wang et al. 2014) have identified a brown adipocyte progenitor population in BAT that is marked by myogenic factor 5 (Myf5)-Cre and expresses platelet-derived growth factor α (Pdgfrα) and Ebf2. These cells emerge at embryonic day 10.5 (E10.5) and are devoid of MyoD at this stage, suggesting that brown adipocyte lineage commitment has already occurred. (B) Tissue-resident adipose precursors in adult mice: Adipose precursor populations have been identified in multiple tissues and are listed as they were identified and characterized. There is likely a degree of overlap in the populations. Additional populations may exist based on published lineage tracing results.

Figure 2.

Tracking de novo adipocyte differentiation using the MuralChaser model. (A) Genetic alleles comprising the MuralChaser lineage tracing system. In the presence of doxycycline (DOX), rtTA activates Cre expression. Cre excises the loxP-flanked membrane tdTomato cassette and allows constitutive activation of membrane GFP (mGFP) reporter expression. (B) “Pulse-chase” lineage tracing approach. Doxycycline-containing food was administered to MuralChaser mice for 9 d to label Pdgfrβ⁺ cells (“pulse”). Animals were then switched to a high-fat diet (HFD) or chow diet for 8 wk in the absence of doxycycline (chase). mGFP⁺ adipocytes represent de novo differentiated fat cells formed during the 8-wk period. (C,D) Administration of doxycycline to MuralChaser mice for 9 d resulted in doxycycline-dependent mGFP labeling (arrowhead) of Pdgfrβ⁺ cells lining the endothelium (CD31⁺) of adipose tissue (“pulse”). (E,F) mGFP labeling was not found in mature adipocytes (perilipin⁺). (G,H) Following 8 wk of high-fat diet feeding, numerous mGFP⁺ perilipin⁺ adipocytes were observed (arrows). These cells represent de novo differentiated adipocytes formed during the 8-wk period. Portions of this figure were reproduced with data from Vishvanath et al. (2016), with permission from Elsevier.