New Wnt+ Adipocyte Population and Their Role in the Regulation of Metabolic Homeostasis

Role of Adipocytes in Metabolic Homeostasis

Adipose tissue, consisting of white adipose tissue (WAT) and brown adipose tissue (BAT), is a key regulator of systemic energy and glucose homeostasis. White adipose tissue (WAT) primarily functions as a site for energy storage, while brown adipose tissue (BAT) specializes in dissipating energy as heat through thermogenesis, collectively contributing to the maintenance of systemic energy balance and metabolic homeostasis.

In addition to regulating homeostasis, adipose tissue also exerts influence as an endocrine organ, producing various bioactive factors to modulate metabolic pathways. Adipocytes, the primary cells of adipose tissue, originate mainly from mesenchymal stem cells (MSCs) found in bone marrow and adipose tissues. The dysfunction of adipocyte function is associated with obesity and related disorders like type 2 diabetes and cardiovascular disease. Many studies have focused on understanding adipogenesis, adipose tissue physiology and pathophysiology in hopes of identifying potential therapeutic targets for understanding and treating obesity-related disorders.

New Population of Adipocytes Identified

In a recent publication, Liu and Colleagues describe a novel population of Wnt+ adipocytes in mouse models, which exhibit persistent activity of the Wnt/β-catenin signaling pathway. The canonical Wnt/β-catenin signaling pathway is known to play important roles in adipocyte lipid metabolism and adipose tissue function. The authors use single-cell transcriptomics (RNA sequencing) and chromatin accessibility profiling assays (transposase-accessible chromatin sequencing) to compare this population to classical adipocytes and explore their functional characteristics with respect to metabolic homeostasis.

These adipocytes, identified using a Tcf/Lef-GFP reporter allele, demonstrate high metabolic and thermogenic characteristics and were found to be present in both embryonic and adult mouse fat depots. Unlike classical adipocytes, Wnt+ adipocytes maintain activation of the Wnt/β-catenin signaling pathway independently of Wnt ligands and receptors, relying instead on the insulin-induced AKT/mTOR pathway for cell survival. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes are required for adaptive thermogenesis. They convert directly into beige adipocytes and are also required for beige fat recruitment under cold exposure conditions, demonstrating both cell autonomous and non-cell autonomous thermogenic roles.

Additionally, gain- and loss-of-function studies were executed to evaluate the potential physiological impact of Wnt+ adipocytes on whole-body glucose homeostasis. Mice with targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied Wnt+ adipocytes showed enhanced glucose utilization suggesting the importance of Wnt+ adipocytes in systemic glucose homeostasis.

The authors further investigated whether the Wnt+ adipocytes are present in the human system. They utilized human bone marrow derived MSCs from Lifeline Cell Technology and transduced the cells with a lentiviral reporter construct containing a reporter gene to monitor Wnt/β-catenin signaling activity. These MSCs were then cultured under specific conditions: either in pro-adipogenic induction medium (Lifeline Cell Technology, LL-0059) to promote adipocyte differentiation or in a pro-osteogenic induction cocktail (Lifeline Cell Technology, LM-0023) to serve as a positive control for Wnt/β-catenin signaling activity. Under the pro-adipogenic medium, the authors observed GFP-tagged adipocytes induced from the transfected BMSCs, indicating the differentiation of Wnt+ adipocytes from human stromal cells. Together, these results suggest that Wnt+ fat cells appear to constitute a widespread adipocyte population that originates from embryonic stage and exists in mice and possibly in humans.

In summary, these studies have uncovered a unique adipocyte population involved in regulating beiging in adipose tissues and maintaining systemic glucose homeostasis that is distinct from the classical adipocytes at the molecular and genomic levels. The potential existence of this population in humans suggests it could serve as a promising therapeutic target for metabolic diseases. Further investigations into the mechanisms governing the function of Wnt+ adipocytes offer potential avenues for developing novel therapeutic strategies to address metabolic disorders like obesity and diabetes.

Lifeline Cell Technology Products to Support Adipocyte Research

The Lifeline® catalog contains MSCs derived from different tissue sources as well as complete media kits to support their growth and differentiation to power your stem cell research:

• Normal Human Mesenchymal Stem Cells — Wharton’s Jelly
• Human Mesenchymal Stem Cells — Adult
• Normal Mesenchymal Stem Cells — Human Bone Marrow
• Normal Human Pre-Adipocyte Cells
• StemLife MSC Medium Complete Kit
• StemLife MSC-BM Bone Marrow Medium Complete Kit

At Lifeline, we’re passionate about sharing the latest advancements in research on our blog. If you’ve utilized Lifeline’s cells and/or media in your studies, we’d love to hear from you! Your publication could be featured next!