Extracellular Matrix Remodeling and Mechanical Stresses as Modulators of Adipose Tissue Metabolism and Inflammation - The Mechanobiology of Obesity and Related Diseases - page 111

Fig. 1 A sustained positive energy balance, e.g. due to a high-fat diet, can lead to progressive
lipid loading and enlargement of adipocyte size. Hypertrophy often precedes deposition of excess
fibrillar ECM proteins (shown as bold black lines), notably collagen type I, leading to fibrosis and
tissue stiffening. Pressure to expand against a stiffer ECM can result in an increase in compressive
stress (red arrow) experienced by the adipocytes. Alternatively, biophysical interactions between
the ECM and the expanding cellular membrane (shown as blue lines surrounding each adipocyte)
can give rise to increased shear and/or stretch induced tension (red double-sided arrow). The
combination of physical constraint against cellular expansion and various mechanical stresses can
lead to metabolic changes, notably enhanced lipolysis and free fatty acid (FFA) efflux. In addition,
the mechanical stresses could activate mechanotransduction pathways leading to the secretion of
immune cell recruitment factors such as monocyte chemoattractant protein-1 (MCP-1), which in
turn promotes a pro-inflammatory state in the adipose tissue. As activated macrophages have been
shown to stimulate collagen type I synthesis in preadipocytes (via factors that remain to be
elucidated), there is an intriguing possibility for a positive feedback that worsens the fibrosis
factor that could influence the mechanism is the extent of the strain. For example, a
recent study found that the inhibitory effect of cyclical stretching (0.5 Hz for 48 h)
correlated with peak strain of 10 % and decreased with stretch thereafter, with 2 %
strain achieving only partial inhibition compared to 10 % strain, and 0.5 % strain
having little effect [ 56 ]. Taken together, it could be concluded that dynamic
mechanical loading suppresses adipogenic differentiation of preadipocytes, pri-
mary MSCs and multipotent cell lines, though the inductive loading parameters
and signaling pathways involved need further investigation.
Unlike dynamic loading effects, static mechanical stretching has been shown to
enhance adipogenic differentiation. Shoham et al. found that applying a static
tensile strain of 12 % to 3T3-L1 preadipocytes significantly increased the rate of
adipogenesis as assessed by the appearance of cells containing visible lipid
droplets [ 57 ]. After approximately two weeks of sustained static stretching, the
differentiated adipocytes also contained significantly larger and greater numbers of
lipid droplets. The elevation in mean lipid droplet diameter persisted through day
28 following induction of differentiation. A subsequent study by the same research
group showed that the effects of static stretching depended on the magnitude of the