Mechanical Stretching and Signaling Pathways in Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 34

MSCs and preadipocytes. These results imply that the mechanical stimulation
would modulate the adipose tissue functions through the bidirectional control of
adipocyte renewal, adiposity, endocrine function of adipocytes, and fine-tuning of
drug actions.
1 Introduction
The adipose tissue is complex and is composed of multiple cellular compartments
having heterogeneous functions that presumably arise from developmentally dif-
ferent cell lineages [ 1 ]. Adipocytes are the primary cellular component in the
adipose tissue, and their excessive growth, differentiation and hypertrophy are
fundamental processes of obesity. Mature adipocytes are generated among cells
from a pre-existing pool of the adipocyte progenitor (preadipocytes or adipo-
blasts), which are present irrespective of age [ 2 ]. Therefore, from a pathophysi-
ological point of view, both the proliferation and differentiation of preadipocytes
together with excessive hypertrophy of adipocytes and adiposity are significant
issues in obesity.
As we are aware, the recent remarkable progress in adipogenesis and related
research fields provides detailed models concerning cellular and molecular
mechanisms of adipogenesis, and excellent publications [ 1 - 5 ] are available which
give an overview of adipogenesis from stem cell to mature hypertrophied adipo-
cytes. Since biological responsiveness of our body to a variety of physical stimuli,
including gravity-force, exercise or moving, as well as hemodynamic forces, have
been well-recognized, the research concerning the molecular and cellular basis of
the mechanosensing and subsequent intracellular signaling (hereafter referred to as
mechanotransduction) has been preceded by research into the force-receiving and/
or the force-generating cells/tissues such as musculoskeletal, cardiovascular, car-
tilage and connective tissues. Adipocytes have been generally regarded as having a
mesenchymal/mesodermal origin [ 1 , 6 , 7 ], although recent lineage-tracing studies
suggest that the origin of adipocytes is likely to be somewhat complex [ 8 , 9 ].
Nevertheless, significant interest has been focused on the mechanoresponsiveness
and mechanotransduction of adipocytes and the progenitor cells, having adipo-
genic competencies, presumably due to the pathophysiological and technological
aspects related to obesity research and regenerative medicine. A comprehensive
review of the mechanotransduction in adipocytes was recently published by
Shoham and Gefen [ 10 ].
As we have previously described, recent advances in adipocyte research have
established that adipose tissue not only serves as a means of energy storage in the
form of triglycerides but also exerts secretory/endocrine functions; adipocytes also
play a pivotal role in the secretion of hormones and cytokines/adipokines, which
causes chronic low-grade inflammation in obese adipose tissues [ 11 ]. We recently
described that mechanical stress acts not only on energy storage function via cell