The Vicious Cycle of Estrogen Consumption and Obesity: The Role of Mechanotransduction - The Mechanobiology of Obesity and Related Diseases - page 87

and overgrowth of WAT leads to obesity and related chronic co-morbidities, e.g.
hyperlipidemia, high blood pressure, carbohydrate intolerance and diabetes, coro-
nary atherosclerotic heart disease and several types of cancer [ 20 , 30 ]. The influence
of estrogen production and consumption in western diets on adipocytes will be
discussed here, as well as the relevant mechanotransduction phenomena in adipose
cells and tissues. In addition, we will review the up-to-date literature focusing on
mechanical behavior and properties of adipose tissues and cells, and provide some
new insights and perspectives in this regard.
2 Development and Structure of Adipose Tissue
There are two types of adipose tissues in humans: white and brown. The WAT is
responsible for maintaining whole-body energy homeostasis by storage and
mobilization of highly energetic molecules in periods of positive and negative
energy balances, respectively. The brown adipose tissue (BAT) specializes in rapid
generation of heat during cold exposure and certain diets [ 7 , 8 , 9 , 40 , 73 , 74 ]. Fetal
adipose tissue composes both brown and white adipose tissues, but the majority of
the tissue is BAT as it ensures that the newborn would effectively adapt to the
(colder) extrauterine environment [ 19 , 40 , 74 ]. Adipose tissues develops as early as
during the 14-24th weeks of gestation where the critical development period is
through the second trimester [ 54 ]. Fat formation starts in the head and neck, and
rapidly progresses to the trunk and limbs [ 54 ]. Ultimately, BATs are mainly
positioned around central organs (i.e., perirenal and pericardial), where the majority
of these depots are gradually replaced by WAT after birth [ 74 ], to facilitate
mobilization of sufficient lipids and provide readily available large amounts of
energy which is required for non-shivering thermogenesis [ 74 ]. Considering that
obesity and the resulted metabolic and cardiovascular complications are associated
with accumulation of WAT [ 8 , 40 ], we focus on WAT in this chapter.
WAT is mainly located subcutaneously (inguinal, dorsosubcutaneous and
interscapular) dermally, and intraperitoneally (mesenteric, omental, perirenal,
retroperitoneal, epididymal and parametrial) [ 30 ]. The fat mass in lean adults is
9-18 % and 14-28 % of the total body weight in males and females, respectively
[ 7 ]. The majority of the cells in WAT are adipocytes, which are spherical cells
with a variable size (diameter *35-100 lm) [ 36 ]. Adipocytes contain one or more
lipid droplets (LDs) containing primarily triglycerides [ 40 ]. The LDs typically
accounts for more than 90 % of the cell volume [ 30 , 58 ]. The triglycerides storage
within the LDs in the adipocytes are responsible for maintaining the whole-body
energy balance that controls fat deposition (i.e. lipogenesis) and fat mobilization
(i.e. lipolysis) [ 21 ]. For this reason, adipocytes are important in the regulation of
energy metabolism and lipid homeostasis. Other than adipocytes, stromal vascular
cells are also present in WAT, including endothelial cells, pericytes, preadipo-
cytes, mast cells, and immune cells [ 42 ]. The ECM of WAT includes stromal
extracellular matrix (ECM) and a basement membrane (BM) [ 6 ]. The stromal