The role of perivascular adipose tissue and infiltrating macrophages in vascular dysfunction with inflammatory bowel disease
Authors:   , Jenkins Samuel Willis, III 
Published: May 2023

Historically, adipose tissue (AT) throughout the body has been categorized as either brown adipose tissue (BAT) or white adipose tissue (WAT). These categories are determined by color, physical characteristics, and physiological functions of the adipocytes of the tissue. WAT is the predominant subtype found in humans with two major depot types: subcutaneous WAT under the skin and visceral WAT, which surrounds the internal organs (Richard et al., 2000). Subcutaneous WAT is located under the skin and acts as a protective barrier against infections, an insulator of body heat and protection against external mechanical stress. The adipocytes in WAT are generally a sphere-shaped cell (Richard et al., 2000; Trayhurn & Beattie, 2001). Because of the single large lipid droplet within the cell, the normal cell organelles are pushed to the cell's periphery. White adipose tissue has a large capacity for lipid storage, thus contributing to its dysfunctional involvement in obesity and dyslipidemia. Further, its structural plasticity allows rapid changes in adipocyte size and/or number (i.e., hypertrophy vs hyperplasia) based on global and local metabolic conditions (Sakers et al., 2022). Regardless of location, WAT was originally thought to function only in energy homeostasis, by taking up excess lipids and store them as triglycerides or breaking them down and releasing the lipids as fatty acids via de novo lipogenesis (Richard et al., 2000; Trayhurn & Beattie, 2001). However, the discovery of leptin in 1990 quickly changed this limited thinking (Zhang et al., 1994). Continued discovery of even more adipose-derived factors, or adipokines, highlighted WAT as a dynamic endocrine tissue that plays an active role in both health and disease. Adipokines include hormones, pro- and anti-inflammatory cytokines, and other proteins with a ride range of global and tissue-specific effects. Overall, adipose research now shows that WAT is involved in inflammation, metabolism and endocrine/paracrine signaling. Brown adipose tissue (BAT) functions as a thermal regulator via non-shivering thermogenesis (Cannon & Nedergaard, 2004). As a specialized AT, BAT represents a relatively small proportion of total adipose and functions as a thermal regulator via nonshivering thermogenesis. There are six anatomic regions that are considered activated BAT depots --cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-- with a majority of all activated BAT concentrated in a continuous layer within the upper torso (Leitner et al., 2017). A specialized, BAT-specific protein called uncoupling protein 1 (UCP1) mediates the uncoupling of mitochondrial respiration necessary for this thermogenesis (Richard et al., 2000). This allows for heat generated by the BAT to dissipate. Brown adipose also contains lipid droplets, but they are smaller than those in WAT and dispersed throughout the cell along with an increased number of iron-containing mitochondria in comparison to white adipose, which gives the tissue its brownish hue (Cannon & Nedergaard, 2004). BAT is found in large quantities in mammals postnatally and during hibernation. In humans, it was initially thought that brown adipose was only present in infants, however it has been found that adult humans have BAT depots with changes to BAT activity occurring during times of external environmental change (Richard et al., 2000). Recently, another phenotype of adipose has been described. Beige adipose tissue shares similar characteristics and function to both brown and white adipocytes. They are thought to develop from a subpopulation of preadipocytes or from the "browning" of WAT into a "browner" phenotype, caused by the high iron-containing mitochondria. The result is an adipocyte with large lipid droplets, increased mitochondria, and protection against metabolic dysfunction in comparison to WAT adipocytes (Cannon & Nedergaard, 2004). The beige phenotype is relatively unstable, and beige adipocytes often re-whiten, becoming indistinguishable from WAT that never underwent the browning process (Mulya & Kirwan, 2016).