Research Area

Adipokine


The traditional concept is that adipose tissue is an inert tissue that functions as storing fat, supplying energy and insulation, absorbing shock, regulating body temperature, filling and fixing. However, in recent years it has been observed that adipose tissue is also an endocrine organ with active metabolism and complex functions. The factors that are widely affected by the secretion of adipose tissue and regulate the body's energy metabolism are called adipokines. This factor plays an important part in obesity, cardiovascular disease, immunoreaction and blood glucose regulation. However, with the widespread use of this term, its meaning has also been expanded. Current adipocytokines can represent cytokines, acute phase reactants, growth factors, other inflammatory mediators, hormones secreted by adipose tissue (such as leptin), and other chemical messengers.

There are many kinds of adipokines. According to the function and source adipokines can be divided into:

Energy balance and metabolism

Inflammation

Thrombosis and hypertension

Growth factors

Brown fat

The structure and function of some adipokine

Leptin

Figure 1. The crystal structure of leptin.

Leptin is a protein hormone with a molecular weight of 16 kDa and is secreted mainly by adipose tissue. Peripheral leptin can enter the central nervous system(CNS) and cerebrospinal fluid, and it acts on specific regions of the brain, such as the hypothalamus or hippocampus. In addition, not only leptin can be transported to the CNS, but some studies suggest that human and rat's brain also produce leptin (such as the hypothalamus, cerebral cortex, cerebellum). Leptin crosses the blood-brain barrier mainly through the action of leptin receptor A; and other transport mechanisms have still not been studied.

Leptin regulates food intake and energy expenditure, improves insulin sensitivity, promotes lipolysis, and inhibits fat formation. Leptin is currently the most widely studied, and the adipokines involved in brain structure and function have a certain effect on brain-related cognition and aging.

Adiponectin

Figure 2. The crystal structure of adiponectin.

Adiponectin (ACRP30) mainly exists in three forms: trimer, hexamer, and high molecular weight polymer; it can regulate CNS and peripheral inflammation, energy consumption, food intake, and some metabolic processes, including glucose regulation and fatty acid catabolism. It is an effective insulin sensitizer, and circulating concentrations are inversely related to insulin, metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease.

Apelin

Apelin (also known as APLN) is a peptide that in humans is encoded by the APLN gene. Apelin is the endogenous ligand for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed in various organs such as the heart, lung, kidney, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma.

Chemerin

Chemerin is a chemoattractant protein that acts as a ligand for the G protein-coupled receptor CMKLR1 (also known as ChemR23). It is a 14 kDa protein secreted in an inactive form as prochemerin and is activated through cleavage of the C-terminus by inflammation and coagulation serine proteases.

In humans, chemerin mRNA is highly expressed in white adipose tissue, liver and lung while its receptor, CMKLR1 is predominantly expressed in immune cells as well as adipose tissue. Because of its role in adipocyte differentiation and glucose uptake, chemerin is classified as an adipokine.

IL-6

Figure 3. The crystal structure of IL-6.

Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. For its function, IL-6 is an important mediator of fever and of the acute phase response. It is capable of crossing the blood-brain barrier and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body's temperature setpoint. As it can be produced by adipocytes, IL-6 is classified as an adipokine.

MCP-1

Figure 4. The crystal structure of MCP1.

Monocyte chemotactic protein 1 (MCP1) is also referred to as the chemokine (C-C motif) ligand 2 (CCL2) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection. MCP-1 may represent a molecular link in the negative cross-talk between adipose tissue and skeletal muscle assigning a completely novel critical role to CCL2 besides inflammation.

PAI-1

Figure 5. The crystal structure of PAI-1.

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene. It's main function entails the inhibition of urokinase plasminogen activator (uPA), an enzyme responsible for the cleavage of plasminogen to form plasmin. PAI-1 is mainly produced by the endothelium (cells lining blood vessels), but is also secreted by other tissue types, such as adipose tissue.

RBP4

Figure 6. The crystal structure of RBP4.

Retinol binding protein 4, also known as RBP4, is a protein that in humans is encoded by the RBP4 gene. This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, which prevents its loss by filtration through the kidney glomeruli.

TNFα

Figure 7. The crystal structure of TNF.

Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. TNFα is mainly produced by the macrophages, but adipose tissue also can secrete the factor.

Visfatin

Figure 8. The crystal structure of visfatin.

Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the NAMPT gene. This protein is the rate-limiting enzyme in the Nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide in mammals to enable NAD+ biosynthesis. The protein is an adipokine that is localized to the bloodstream and has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. The protein is highly expressed in visceral fat and serum levels of the protein correlate with obesity.

Omentin

Figure 9. The crystal structure of omentin.

Omentin is one of human intelectins, and it was encoded by ITLN1 genes. It has also been shown to bind lactoferrin, but the functional consequence has yet to be elucidated. Additionally, hIntL-1 is a major component of asthmatic mucus and may be involved in insulin physiology as well.

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