Visfatin

Visfatin is a protein (~52 kDa, ~471-491 amino acids) also known as nicotinamide phosphoribosyl transferase (NAMPT), is a key enzyme in NAD⁺ salvage metabolism. The protein is encoded by the NAMPT gene (nicotinamide phosphoribosyltransferase) located on chromosome 7q22.3.

Visfatin occurs in two forms:

• Intracellular (iNAMPT), essential for NAD⁺ synthesis.
• Extracellular (eNAMPT), which acts like a hormone, as an adipokine or cytokine.

Visfatin is mainly produced by visceral adipose tissue. Hence the name "visfatin". The protein is also expressed in leukocytes, muscle, liver, heart and brain cells.

Functions in the body

• Enzymatic role (iNAMPT): Forms the central step in NAD⁺ biosynthesis via nicotinamide → nicotinamide mononucleotide (NMN) . NAD⁺ is essential for many proteins (sirtuins, PARPs, CD38) and regulates cell metabolism, repair and ageing .
• Hormone-like effect (eNAMPT): Has an insulin-mimetic effect: binds to the insulin receptor (different binding site) and stimulates glucose uptake in muscle & liver cells, lowers blood glucose levels in animal models. Activates AMPK p38 MAPK signaling pathway in muscle cells, promotes GLUT4 translocation, even in combination with insulin synergistically.
• Immune and inflammatory modulation: Visfatin promotes release of cytokines such as IL 1β, TNF α, IL 6. Supports proliferation of leukocytes, suppresses apoptosis, generates ROS and promotes vascularization .
• Obesity and insulin resistance: Visfatin levels increase in obesity; role in inflammation and impaired glucose metabolism .
• In type 2 diabetes: Increased blood levels; studies show links with insulin resistance and beta cell dysfunction.
• In cardiovascular disease: Visfatin as a potential marker for atherosclerosis and cardiovascular risk; promotion of plaque inflammation and endothelial function .
• Malignancies: Visfatin is upregulated in certain tumors (e.g. prostate, colon). It plays a possible role in proliferation and survival of tumor cells (Mohammadi M et al. 2019).

Visfatin and psoriasis: Visfatin levels are elevated in the serum of patients with psoriasis and show a positive correlation with the severity of the disease (Kanda N et al. 2011). Visfatin enhances TNF-alpha-triggered inflammatory responses in keratinocytes by upregulating CXCL8, CXCL10, CCL20 and antimicrobial peptides (Chyl-Surdacka KM et al. 2020; Hau CS et al. 2013; Kanda N et al. 2011).

Systemic scleroderma: The adipokines chemerin and visfatin are proinflammatory cytokines and may serve as novel markers of inflammation in systemic scleroderma. Chemerin could also establish a link between inflammation and skin and lung fibrosis (Sawicka K et al. 2019).

1. Chyl-Surdacka KM et al. (2020) Assessment of visfatin concentrations in the serum of male psoriatic patients in relation to metabolic abnormalities. Adv Clin Exp Med 29:79-84.
2. Hau CS et al. (2013) Visfatin enhances the production of cathelicidin antimicrobial peptide, human β-defensin-2, human β-defensin-3, and S100A7 in human keratinocytes and their orthologs in murine imiquimod-induced psoriatic skin. Am J Pathol. 182:1705-1717.
3. Kanda N et al. (2011) Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes. Endocrinology. 152:3155-3164).
4. Mohammadi M et al. (2019) Circulating visfatin levels and cancers risk: A systematic review and meta-analysis. J Cell Physiol 234:5011-5022.

5. Sawicka K et al. (2019) Visfatin and chemerin levels correspond with inflammation and might reflect the bridge between metabolism, inflammation and fibrosis in patients with systemic sclerosis. Postepy Dermatol Alergol 36:551-565.