The Vicious Cycle of Estrogen Consumption and Obesity: The Role of Mechanotransduction - The Mechanobiology of Obesity and Related Diseases - page 92

genders. For example, [ 16 ] found that ER-b levels were significantly greater in
mature human adipocytes from women with respect to men. In addition, ER-a
mRNA expression was 40-times greater in adipocytes than in preadipocytes from
women [ 16 ]. Considering that estrogen signaling mechanisms involve mainly
activation of the two types of the ERs (a and b), the different documented
responses to estrogen could have been expected.
6 Mechanotransduction in Adipocytes
Adipose tissues are weight-bearing structures exposed to compound mechanical
loading: tensile, compressive and shear strains/stresses, which are associated with
gravity (bodyweight loads) and weight-bearing [ 44 ]. For example, at a continuum
scale, adipose tissues of the buttocks (overlying the gluteus muscles) are statically
loaded during sitting with peak tensile, compressive and shear strains of *30,
*45 and *40 %, respectively [ 44 ]; a lying posture induces peak strains that are
approximately half these magnitudes at the same anatomical location. During
dynamic loading, e.g., during a physical exercise, strains in adipose tissues could
reach even greater peak magnitudes. Hence, it is important to determine whether
adipocytes are mechanosensitive, i.e., whether the adipose conversion process is
influenced by chronic and/or transient mechanical stimulations. Indeed, adipocytes
are currently becoming recognized as mechanoresponsive cells, with increasing
evidence for that from several model systems designed at different dimensional
scales (i.e. cell cultures, animal models and human studies) (see a detailed review
in this regard in [ 68 ]. At the cellular level, mechanical stimuli were found to
influence both the commitment of cells to the adipocyte phenotype and their
differentiation processes [ 5 , 14 , 33 , 61 - 63 , 68 , 75 - 78 ]. In general, dynamic
loading modes, including cyclic stretching or vibrations, were found to suppress
adipocyte differentiation in cells from different sources, e.g. preadipocytes, mes-
encymal stem cells and adipose tissue stromal cells [ 5 , 14 , 33 , 61 - 63 , 75 - 78 ].
However, different signaling pathways, e.g., the MAPK/ERK or the TGFb1/Smad
were found to be activated in response to the mechanical stimuli induced in these
studies. Static loads appear to have a dual effect on adipogenesis, where static
stretching accelerated differentiation [ 29 , 43 , 68 ] but static compression [ 32 ]
impeded it. Here again, multiple different signaling pathways were found to be
involved in the process, e.g., the MAPK/MEK [ 68 ] or the Rho/Rho-Kinase [ 29 ]. In
line with the in vitro (cell culture model) results, dynamic loading delivered to
native adipose tissues in animals as well as in humans was generally found to
suppress adipogenesis and reduce body fat, whereas static loading promoted adi-
pogenesis [ 37 , 45 , 46 , 53 ]. Combining these studies, biomechanical properties and
mechanical loading regimes of adipose tissues and cells cannot be ignored in the
research of obesity and related diseases.