Biomedical Engineering Reference
In-Depth Information
mechanical influences in isolation from confounding biochemical influences
present in vivo. In this regard, we expect engineered ECM and advanced biore-
actors to serve as valuable model systems to dissect the effects of mechanical
stresses under controlled chemical conditions.
1 Introduction
In adult humans, body fat essentially consists of white adipose tissue (WAT).
While recent findings from 18F-fluorodeoxyglucose (18F-FDG) positron emission
tomography (PET) studies indicate the presence of functional brown adipose tissue
(BAT) [
1
], the reported amounts represent a quantitatively minor fraction of total
body fat. The core metabolic function of WAT is to store excess nutrients as
esterified lipids (i.e. triglycerides, TGs) and to mobilize these stores during fasting.
Until about 20 years ago, WAT has historically been viewed as passive storage
depots. However, discoveries of WAT-derived hormones with systemic effects,
notably leptin [
2
], have fundamentally redefined the physiological role of the
tissue as an active site of metabolic regulation for the whole body [
3
]. In addition
to endocrine factors, adipose cells also produce a host of cytokines and other
signaling molecules that act in an autocrine or paracrine manner to regulate the
tissue's architecture and function.
The bulk of WAT cellular mass comprises metabolically active lipid-laden
white adipocytes, held in a dense network of fibrous extracellular matrix (ECM)
proteins. Other major cell populations include vascular endothelial cells, undif-
ferentiated stromal cells with the potential to differentiate into adipocytes, and
resident immune cells. Differentiated adipocytes express metabolic pathways for
fatty acid uptake, de novo fatty acids synthesis, esterification, and breakdown of
TGs into free fatty acids. Adipocytes are also the dominant source of adipokines.
The core biochemical functions of the WAT thus reside in the adipocytes. How-
ever, the other cell populations directly influence these functions, especially
through their contributions to tissue remodeling. For example, undifferentiated
stromal cells are a major source of ECM protein synthesis, especially collagens. In
vivo, almost the entire adipocyte volume is filled by a single large lipid droplet,
which expands or shrinks depending on the body's energy balance. Chronic
overfeeding can lead to significant expansion of adipocyte volume, termed
hypertrophy, to accommodate the storage of excess nutrients as lipids. This
expansion requires a reorganization of the surrounding ECM as well as neovas-
cularization for adequate oxygen supply. Hypertrophic expansion cannot proceed
without limit; it is thought that recruitment and differentiation of locally resident
precursor cells may also be necessary to accommodate additional lipid stores.
Adipocyte hypertrophy, especially in the context of obesity, also correlates with
accumulation of pro-inflammatory immune cells in WAT, which in turn underpins
tissue insulin resistance and other metabolic alterations associated with obesity-
related metabolic diseases.
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