542
F. Tourniaire et al.
The excess of fat mass occurring during obesity is characterized by an expansion of adipose tissue mediated by hypertrophia and/or hyperplasia of adipocytes
(Arner et al. 2010), which is linked to the complex and tightly regulated adipogenesis. This process has been intensely studied, and the temporal sequences as
well as transcriptional regulators involved have been identified. Among them, the
nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and the
CCAAT-enhancer-binding protein (CEBPs) families are considered as transcriptional
regulators of adipogenesis (Farmer 2006). Through this mechanism the adipose tissue
is able to participate in energy homeostasis, allowing the storage of excess energy as
triglycerides (lipogenesis) and the release of energy as fatty acids (lipolysis). This
balance is tightly regulated, and dysregulation may result in body weight gain or
loss.
In addition, adipose tissue is also regarded as an endocrine tissue producing not
only free fatty acids but also a large variety of hormones, cytokines, chemokines,
miRNA, as well as adipokines and growth factors, acting on many physiological processes. Indeed, adipose tissue secretes approximately 50 biologically active
proteins acting in an autocrine, paracrine, and/or endocrine fashion. Leptin (Friedman
2014) and adiponectin (Ruhl and Landrier 2015) are among the most studied. Both
adipocytes and cells belonging to the stromal vascular fraction of adipose tissue,
especially macrophages, are able to produce and secrete adipokines. Obesity triggers a chronic low-grade inflammation which is associated to abnormal secretion
of cytokines (Gregor and Hotamisligil 2011), chemokines (Tourniaire et al. 2013),
miRNA (Karkeni et al. 2016, 2017), acute phase proteins, and other mediators of
the immune response together with the activation of inflammatory signaling pathways (Gregor and Hotamisligil 2011; Olefsky and Glass 2010). Adipose tissue is a
major contributor to the chronic inflammatory response. The regulation of molecules
secreted by adipose tissue is multifactorial and is linked to several physiopathological
disorders, including (i) increased levels of circulating free fatty acids, (ii) hypoxia
of hypertrophied adipose tissue, (iii) systemic and local oxidative stress, (iv) endoplasmic reticulum stress, and/or (v) the production of inflammatory cytokines. All
these types of stress converge toward signaling pathways involving c-Jun aminoterminal kinase (JNK) and IκB kinase β (IKKβ) (Gregor and Hotamisligil 2011;
Olefsky and Glass 2010). A large part of this inflammatory state is mediated by
the increased number of infiltrated macrophages that occurs during the expansion
of adipose tissue (Weisberg et al. 2003). Such infiltration has been positively correlated with adiposity, adipocyte size, and insulin resistance (Bourlier and Bouloumie
2009). Indeed, macrophages interfere with adipocyte function through the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which can lead
to insulin resistance, modify adipokine secretion, and lead to an excess of free fatty
acid secretion through increased lipolysis and diminished lipogenesis (Cornier et al.
2008), participating thus to the establishment of obesity-associated disorders, such
as insulin resistance.
Beside this effect of inflammatory state on adipocyte and adipose tissue function,
it has also been that metabolic inflammation is associated to neuro-inflammation.
F. Tourniaire et al.
The excess of fat mass occurring during obesity is characterized by an expansion of adipose tissue mediated by hypertrophia and/or hyperplasia of adipocytes
(Arner et al. 2010), which is linked to the complex and tightly regulated adipogenesis. This process has been intensely studied, and the temporal sequences as
well as transcriptional regulators involved have been identified. Among them, the
nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and the
CCAAT-enhancer-binding protein (CEBPs) families are considered as transcriptional
regulators of adipogenesis (Farmer 2006). Through this mechanism the adipose tissue
is able to participate in energy homeostasis, allowing the storage of excess energy as
triglycerides (lipogenesis) and the release of energy as fatty acids (lipolysis). This
balance is tightly regulated, and dysregulation may result in body weight gain or
loss.
In addition, adipose tissue is also regarded as an endocrine tissue producing not
only free fatty acids but also a large variety of hormones, cytokines, chemokines,
miRNA, as well as adipokines and growth factors, acting on many physiological processes. Indeed, adipose tissue secretes approximately 50 biologically active
proteins acting in an autocrine, paracrine, and/or endocrine fashion. Leptin (Friedman
2014) and adiponectin (Ruhl and Landrier 2015) are among the most studied. Both
adipocytes and cells belonging to the stromal vascular fraction of adipose tissue,
especially macrophages, are able to produce and secrete adipokines. Obesity triggers a chronic low-grade inflammation which is associated to abnormal secretion
of cytokines (Gregor and Hotamisligil 2011), chemokines (Tourniaire et al. 2013),
miRNA (Karkeni et al. 2016, 2017), acute phase proteins, and other mediators of
the immune response together with the activation of inflammatory signaling pathways (Gregor and Hotamisligil 2011; Olefsky and Glass 2010). Adipose tissue is a
major contributor to the chronic inflammatory response. The regulation of molecules
secreted by adipose tissue is multifactorial and is linked to several physiopathological
disorders, including (i) increased levels of circulating free fatty acids, (ii) hypoxia
of hypertrophied adipose tissue, (iii) systemic and local oxidative stress, (iv) endoplasmic reticulum stress, and/or (v) the production of inflammatory cytokines. All
these types of stress converge toward signaling pathways involving c-Jun aminoterminal kinase (JNK) and IκB kinase β (IKKβ) (Gregor and Hotamisligil 2011;
Olefsky and Glass 2010). A large part of this inflammatory state is mediated by
the increased number of infiltrated macrophages that occurs during the expansion
of adipose tissue (Weisberg et al. 2003). Such infiltration has been positively correlated with adiposity, adipocyte size, and insulin resistance (Bourlier and Bouloumie
2009). Indeed, macrophages interfere with adipocyte function through the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which can lead
to insulin resistance, modify adipokine secretion, and lead to an excess of free fatty
acid secretion through increased lipolysis and diminished lipogenesis (Cornier et al.
2008), participating thus to the establishment of obesity-associated disorders, such
as insulin resistance.
Beside this effect of inflammatory state on adipocyte and adipose tissue function,
it has also been that metabolic inflammation is associated to neuro-inflammation.