Biomedical Engineering Reference
In-Depth Information
There is now increasing evidence that mechanistic relationships exist between
adipocyte hypertrophy, tissue remodeling, inflammation, and metabolic altera-
tions. Several biochemical explanations have been proposed to connect tissue
remodeling and inflammation, including hypoxia-induced deposition of excess
collagen [
4
]. However, many questions remain regarding the molecular mecha-
nisms responsible for the structural and functional changes in hypertrophic adipose
tissue. For example, it is not clear whether alterations in adipocyte-ECM inter-
actions play a direct role in bringing about the inflammatory state, and if so, which
pathways contribute to sensing and transducing these alterations. In this context,
the potential roles of mechanical stimuli and their downstream effectors as
mediators of cell-ECM interaction in adipose tissue have not yet been thoroughly
investigated.
The purpose of this chapter is to review recent findings that have begun to shed
light on the biochemical responses elicited in adipose cells by various mechanical
stresses and the signaling pathways that are engaged by these stresses. We begin
by highlighting changes in the composition and architecture of adipose tissue ECM
that closely associate with adipocyte hypertrophy. Next, we briefly describe cor-
related changes in metabolic regulation and inflammatory state of adipose tissue.
We then turn our attention to specific signaling pathways that are activated by
intracellular mechanical stresses that develop with adipocyte hypertrophy, as well
as the effects of extracellularly imposed mechanical stresses such as those that
result from tissue mass expansion or body movement. In reviewing the current
literature, we found that relatively few studies directly investigated the effects of
mechanical cues in isolation from confounding biochemical signals in the context
of adipocyte hypertrophy or obesity. As in vitro systems could represent an
attractive option to control the presentation of mechanical cues under defined
biochemical conditions, we summarize recent advances in utilizing engineered
ECMs and scaffolds to study the differentiation and function of adipocytes. We
close the chapter by suggesting potential uses of the engineered in vitro systems to
carefully deconstruct the complex milieu of biochemical and mechanical cues that
influence adipocyte-ECM interactions in vivo.
2 Adipose Cellular Hypertrophy and ECM Changes
To date, more than 70 ECM proteins have been identified across human and rodent
WAT depots, including 20 subunits of 12 different types of collagen [
5
]. While
questions remain regarding the biological functions of many of the ECM proteins,
there is reasonable consensus regarding the major components and their synthesis
and degradation during adipose tissue development. The dominant component of
fibrous ECM in WAT is type I collagen. The collagen type I molecules exist
mainly as heterotrimers in a triple helix, and are interwoven with each other to
form thick bundles. A basement membrane enriched in collagen type IV surrounds
each adipocyte, and interacts with collagen type I bundles through collagen type V
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