Cytokines in Abnormalities of Glucose and Lipid Metabolism and Bone Metabolism

Cytokines are small molecular peptides or glycoproteins synthesized and secreted by a variety of tissue cells, mainly immune cells. Cytokines mediate cellular interactions and have a variety of biological functions that can be involved in immune diseases, inflammation, and infectious diseases. Some cytokines play a positive role in metabolic activities, while others have negative metabolic effects related to the induction of metabolic dysfunction.

When biochemical processes occur in the body, the accumulation or deficiency of sugars, fats and proteins in the body makes the level of metabolic substances in the body abnormal, which may cause some metabolic diseases.

What is the role of cytokines in the common abnormalities of glucose and lipid metabolism and bone metabolism?

The Role of Cytokines in Abnormal Glucose and Lipid Metabolism

Glucose and lipid disorders are a group of diseases that cause systemic organ damage and hypofunction due to abnormal glucose and lipid metabolism in the body, with the main clinical symptoms being hyperglycaemia, hyperlipidaemia, hepatic lipid accumulation and insulin resistance. Cytokines such as adipokines, hepatokines, inflammatory cytokines, myokines and bone factors contribute significantly to the development of abnormal glucose and lipid metabolism and glucose metabolism (leptin, adiponectin, resistin), insulin sensitivity (leptin, adiponectin, zinc-α2- glycoprotein, ZAG glycoprotein, ZAG), and adipogenesis (bone morphogenetic protein 4) are affected.

Adipose tissue secretes protein substances called adipokines, which can perform a variety of biological functions in an autocrine, paracrine and endocrine manner. For example, they regulate energy intake and energy expenditure, modulate glucolipid metabolism, and provide anti-inflammatory and pro-inflammatory responses. Overall, adipokines regulate the biological responses of different target organs such as the brain, liver, muscle, vascular system, heart, pancreas and immune system. Some adipokines have been shown to affect glucose and lipid metabolism directly or indirectly, as well as insulin sensitivity by modulating insulin signalling.

Leptin promotes fatty acid oxidation by stimulating the phosphorylation and activation of adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK). It also enhances insulin sensitivity in peripheral tissues. In addition, leptin stimulates glucose uptake and prevents the accumulation of lipids in non-adipose tissues.

Lipocalin is a peptide expressed mainly in white adipose tissue (WAT). It is produced in hepatocytes during stress and is negatively correlated with fat mass.

Resistin is a cysteine-rich secretory protein found in plasma. In mice, resistin is mainly synthesised in adipocytes. In humans, resistin is mainly produced by macrophages that infiltrate adipose tissue and peripheral blood mononuclear cells, and is not detected in adipocytes. Resistin has been shown to promote insulin resistance in mouse studies.

The Role of Cytokines in Bone Metabolism

Animal experiments have demonstrated that bone also plays a role in the regulation of glucolipid metabolism. For example, diabetes mellitus is a common disease with abnormal glucolipid metabolism. Diabetes is often accompanied by complex skeletal disorders, such as reduced bone density, easy fracture and delayed repair after fracture. Abnormal bone metabolism may be one of its complications.

So what physiological functions do cytokines play in abnormal bone metabolism?

Elevated levels of adipokine resistin and inflammatory cytokines interleukin-6 and tumor necrosis factor secreted by adipose tissue, and decreased levels of adipokine lipocalin as well as sex hormones and pancreatic precipitins influenced by adipose tissue can affect bone metabolism.

Growth hormone (GH) is one of the regulators of the growth, development and metabolism of the body's tissue cells, and is able to promote cell differentiation and proliferation. It has been suggested that GH acts directly on skeletal cells, but is more often controlled by stimulating the synthesis of IGF-1. Insufficient GH secretion is one of the major causes of osteoporosis in middle-aged and elderly people.

Interleukin-1 (IL-1) has 11 members and is known as the interleukin-1 family. IL-1 directly enhances the activity of osteoclasts and inhibits the apoptosis of mature osteoclasts, prolonging the life span of mature osteoclasts. IL-1 has an important role in the evolution of osteoporosis. IL-1 is an important activator of osteoclasts, an important determinant of bone mineral density and a powerful stimulator of osteoclastic bone resorption.

Interleukin-6 (IL-6) has an important role in the pathogenesis of primary osteoporosis. It regulates bone metabolism by regulating the development and function of osteoclasts and osteoblasts, and elevated levels of IL-6 can be a marker of active osteoclast function in the body. In osteomalacia, multiple myeloma and psoriasis, IL-6 levels are elevated.

Transforming growth factor beta (TGF-β) is widely present in bone tissue. In bone, osteoblasts and chondrocytes can synthesise TGF-β. The concentration of TGF-β in bone tissue is 100 times higher than in other tissues. The highest concentration in bone tissue is TGF-β1. When the concentration of TGF-β in blood decreases, the promotion of bone formation is diminished and bone density decreases, which can lead to metabolic bone diseases such as osteoporosis.

Tumour Necrosis Factor (TNF): TNF-α is a very important osteoclast activator. the inhibitory effect of TNF-α on osteogenesis is manifested by a significant inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblast mineralisation. Pathological bone loss such as age-related osteoporosis, chronic inflammation-induced bone resorption tissues have increased TNF-α.

Insulin growth factor (IGF) includes IGF-Ⅰ and IGF-Ⅱ. IGF-Ⅰ is the most abundant growth factor in bone. IGF-Ⅰ is the most abundant growth factor in bone. IGF-Ⅰ in bone tissue mainly comes from osteoblasts and bone marrow stromal cells, and acts on bone through endocrine, autocrine and paracrine pathways. IGF-Ⅰ can promote osteoblast differentiation, proliferation and recruitment, promote osteoblast collagen and osteocalcin synthesis, and accelerate bone mineralization. Serum IGF-Ⅰ level is mainly regulated by GH, and IGF-Ⅰ concentration is consistent with GH concentration in a wide range. It has also been shown that a decrease in serum IGF-Ⅰ level is closely related to the incidence of fracture, and the level of IGF-Ⅰ can be used as an indicator for fracture risk assessment.

To facilitate the study of the functions played by cytokines in abnormalities of glucolipid metabolism and bone metabolism, Creative Proteomics has developed a variety of cytokine panels based on Luminex technology, capable of detecting multiple markers simultaneously. With only 25-50ul of sample, up to forty protein markers can be detected simultaneously with high sensitivity and wide dynamic detection range. Customized service is available, and multiple factors in the same panel can be combined to meet the needs of more researchers in different research areas.

Reference:

1. Shi, J., Fan, J., Su, Q., & Yang, Z. (2019). Cytokines and abnormal glucose and lipid metabolism. Frontiers in endocrinology, 10, 703.