Adipokines: inflammation and the pleiotropic role of white adipose tissue

Abstract

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFa, IL-1b, IL-6, IL-8, IL-10, transforming growth factor-b, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.

Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours

“…It may be suggested that a lower BMI reflects a more aggressive disease, although this is difficult to define, and may refer to tumour extension, tumour kinetic, tumour biology or treatment sensitivity. The pathophysiological mechanisms involved are still unknown, and a role for adipokines might be hypothesised (Trayhurn and Wood, 2004). Other explanation could be advanced: chemotherapy dose was based on body surface area (mg m À2 ) such that patients with higher BMI may receive a larger total dose of chemotherapy.…”

β-Carotene conversion products and their effects on adipose tissue

“…More than 50 different adipokines have been identified so far, including: adiponectin, leptin, resistin, acylation stimulating protein, fasting-induced adipose factor, enzymes involved in lipoprotein metabolism and various cytokines, chemokines and acute phase proteins [59,62,69,74]. In 2005, vitamin A plasma transporter RBP4 (retinol binding protein-4) of adipose origin was identified as a new adipokine favouring insulin resistance in mice through effects on liver and muscle [79], which are more likely independent of vitamin A.…”

Associations of low-grade inflammation with physical activity, fitness and fatness in prepubertal children; the European Youth Heart Study

“…Observational studies have shown that a state of low-grade inflammation is associated with adiposity in children and adolescents, [3][4][5][6] as it has been shown in adults. 7 Low-grade inflammation is associated with anthropometric measures such as body mass index (BMI) and waist circumference in adolescents, 3,4 but data on children are sparse. Less is known about the association of low-grade inflammation with cardiovascular fitness (CVF) in prepubertal children.…”