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Adipose: Cell Types Composing the Tissue

Adipose tissue is a loose connective tissue with the primary function of storing lipids that can be harvested for energy. This function is performed by adipocytes, which comprise the vast majority of cells in adipose tissue. However, multiple other cell types can be found in adipose tissue; these cells are grouped under the category of the stromal vascular fraction (SVF). Cells of the SVF include preadipocytes, fibroblasts, vascular endothelial and smooth muscle cells, mesenchymal stem cells, endothelial progenitor cells, and immune cells such as anti-inflammatory M2 macrophages and T regulatory cells. An understanding of the cell types in adipose tissue is crucial for many relevant clinical applications, such as approaches to dealing with obesity and also potential therapeutic uses of adipose stem cells for various disease processes.

Function of Adipocytes

“Adipose tissue” often refers to white adipose tissue, which generally comprises around 20 percent (with great variation) of human body mass. In many mammals, including human infants, brown adipose tissue is also present for thermogenic function in the absence of shivering. Human adults also have remnants of brown adipose tissue, generally in the neck or upper chest region, but white adipose tissue is the most prevalent and clinically relevant.

White adipocytes. The majority of white adipose tissue is located either subcutaneously or viscerally, although small deposits can be found in a variety of locations, from within the bone marrow to around the epicardium, within joints and in craniofacial pads. Subcutaneous adipose tissue is located in the hypodermis throughout the body and especially in regions such as the hips, abdomen, or thighs. Visceral adipose tissue is packed in between organs of the abdomen, and is thought to be the most clinically relevant for disease processes such as obesity and type 2 diabetes mellitus. The primary cell type in white adipose tissue is the white adipocyte.

White adipocytes have a distinctive histological appearance of a single (unilocular) large lipid droplet surrounded by a thin layer of cytoplasm with a flattened peripheral nucleus. Multiple hormone and other receptors are present on the surface of white adipocytes; this, coupled with endogenous adipocyte hormone production, gives white adipose tissue tremendous endocrine function in addition to its storage capacities. In particular, white adipocytes play key endocrine roles in energy metabolism and sex hormone levels.

One way that energy metabolism is regulated is through white adipocytes’ synthesis and secretion of leptin, a peptide hormone that inhibits appetite in the hypothalamus. Circulating levels of leptin are proportional to the amount of white adipose tissue in the body, and leptin resistance has been implicated in obesity. Energy metabolism is also regulated by the presence of insulin receptors on white adipocytes, which inhibit lipolysis in the presence of sufficient glucose in the bloodstream.

Adipose tissue or body fat is loose connective tissue composed of adipocytes whose main function aside from insulating the body is to store energy in the form of lipids. The two types of adipose are white adipose tissue (WAT) and brown adipose tissue (BAT). (Wikiversity Journal of Medicine)

Sex hormone levels in the body are influenced by white adipocytes’ ability to synthesize estradiol, via their production of the enzyme aromatase that converts androgens into estrogen. However, the primary function of the white adipocyte overall is to store lipid. Lipid content of adipose tissue overall increases with age, due to hypertrophy of white adipocytes. Although excess energy intake can result in the formation of new adipocytes, weight loss results in merely shrinkage of existing adipocytes rather than a decrease in number.

Brown adipocytes

Brown adipocytes have a greater ratio of cytoplasm to lipid content, and multiple smaller lipid droplets (multilocular) when compared to white adipocytes. The cytoplasm contains multiple mitochondria, which lend to the brown color of the cell and work to generate heat via lipid oxidation. Unlike white adipocytes, brown adipocytes express uncoupling-protein 1 (UCP-1), which drives the generation of heat by dissipating the mitochondrial proton gradient (leading to direct heat production rather than ATP production and storage). Brown adipose tissue in general also exhibits greater vascularization, due to a greater need for oxygen by the mitochondria. Recent research has looked into the possible expression of UCP-1 by white adipose tissue as a method of combating obesity.

Function of Stromal Vascular Fraction

Preadipocytes

Preadipocytes are fibroblast-like cells derived from mesenchymal stem cells. Preadipocytes are committed to the adipocyte lineage and are regularly present in adipose tissue in small quantities, where they serve both to replenish dying adipocytes (adipocyte turnover is around 10 percent per year) and to increase existing adipocyte numbers when energy stores are plentiful. Preadipocytes often reside in close proximity to the vasculature of adipose tissue and express the transcription factor PPAR, which has been identified as essential to adipogenesis. Preadipocytes require a specific, high-lipid microenvironment in order to differentiate into adipocytes; however, in the case of obesity, preadipocyte numbers actually decrease, perhaps as a compensatory mechanism to prevent excess irreversible adipocyte formation.

One of the factors that allow preadipocytes to maintain stable reservoirs of adipogenesis is their expression of telomere reverse transcriptase, which prevents the shortening of telomeres and subsequent DNA degradation over generations of replication. Differing populations of preadipocytes give rise to brown and white adipocytes, and within white adipocytes, there are regional differences as well. For example, visceral preadipocytes take much longer than their subcutaneous counterparts to differentiate and mature into adipocytes; this may explain the hypertrophy and greater lipid accumulation of visceral adipocytes.

A greater amount of lipids in each adipocyte in turn influences the adipokines (signaling proteins from adipose tissue) that are secreted, which can have profound clinical effects. For example, visceral adipocytes secrete much less of the adipokine adiponectin, and this has been shown to decrease insulin sensitivity and ramp up pro-inflammatory processes in visceral adipose tissue compared to subcutaneous. Research on how to alter preadipocyte gene expression, and thereby change adipocyte characteristics, has been relevant both for obesity and also in potential approaches to treating lipodystrophic disorders.

Mesenchymal stem cells

From mesodermal origin, mesenchymal stem cells (MSCs) are present in many different connective tissues, such as within the bone marrow. In the microenvironment of adipose tissue, MSCs generally differentiate into preadipocytes. However, MSCs can still be induced to develop into osteogenic, chondrogenic, myogenic, and other lineages, and have been heralded for their great research potential. Harvested via liposuction, in vitro studies of processed lipoaspirate (PLA) have yielded MSCs that are being studied for their use in autologous stem cell transplant. Human adipose tissue shows great potential for potential stem cell use due to its availability, quantity, and ease of obtainment.

Endothelial progenitor cells

Separate from mesenchymal stem cells, endothelial progenitor cells (EPCs) have been identified that give rise to adipose tissue vasculature. These EPCs are free-circulating and bone marrow derived, and usually present in the SVF in small quantities. They contain angiogenic and/or hematopoietic cell markers. It has been postulated that in obesity, there are greater numbers of EPCs trapped in the adipose tissue rather than free to circulate, and thus angiogenic ability overall is reduced in obese patients. EPCs have also been the subject of much research recently involving potential transplantation to rebuild vessels damaged by atherosclerosis and stenosis.

Immune cells

Both T-regulatory immune cells and macrophages are resident to the SVF. The T-regulatory cells (T-regs) are immune suppressive cells formed from the activation of T cells in the absence of costimulatory signals, and their presence in adipose tissue has shown to be induced by markers generated from MSCs in adipose. T-regs in turn help promote the presence of macrophages. The macrophages present in adipose tissue are interesting in that they possess markers for both pro- and anti-inflammatory processes. On a surface level, adipose tissue macrophages (ATMs) express markers and receptors similar to M2-type macrophages, which promote tissue repair. ATMs, like M2 macrophages, can also be induced to secrete anti-inflammatory proteins like IL-10 and IL-1 receptor antagonist.

However, these same ATMs also secrete inflammatory proteins such as TNF-α, IL-1, and IL-6 in quantities high enough to offset any anti-inflammatory activity by both the ATMs and T-regs. It is postulated that the ATM protein secretion is under the regulation of adipocytes, which also secrete these inflammatory proteins themselves, and both of these processes contribute to the low-grade inflammatory state often present in obesity.

Other cells

Vascular and extracellular matrix cells that are present throughout the body are also found in adipose tissue. Similar to vasculature throughout the body, the vessels of adipose tissue consist of endothelial and smooth muscle cells. These endothelial cells include both ordinary endothelial cells like those found elsewhere and also specialized endothelial cells that appear to be able to induce preadipocyte generation. Fibroblasts also help secrete collagen and other extracellular matrix components that help form the structure of adipose tissue.

Overall, many different cells in adipose tissue have vast potential for further research investigation. Especially with the rise of obesity, there has been a much greater international interest in learning more about the components of adipose tissue and how they can be altered. In particular, MSCs and preadipocytes show promise for future use both in treating obesity and a plethora of other disorders.

Both adipocytes and components of the stromal vascular function are integral parts of adipose tissue, and understanding their functions will be a critical cornerstone of future learning.

Krishna S. Vyas

Nazeeha Jawahir

University of Kentucky College of Medicine

See Also: Adipose: Current Research on Isolation or Production of Therapeutic Cells; Adipose: Development and Regeneration Potential; Adipose: Existing or Potential Regenerative Medicine Strategies; Adipose: Major Pathologies; Adipose: Stem and Progenitor Cells in Adults; Adipose: Tissue Function.