Fibrillin-1 and fibrillin-1-derived asprosin in adipose tissue function and metabolic disorders

Abstract

The extracellular matrix microenvironment of adipose tissue is of critical importance for the differentiation, remodeling and function of adipocytes. Fibrillin-1 is one of the main components of microfibrils and a key player in this process. Furin processing of profibrillin-1 results in mature fibrillin-1 and releases the C-terminal propeptide as a circulating hunger hormone, asprosin. Mutations in the fibrillin-1 gene lead to adipose tissue dysfunction and causes Marfan syndrome, marfanoid progeroid lipodystrophy syndrome, and neonatal progeroid syndrome. Increased TGF-β signaling, altered mechanical properties and impaired adipogenesis are potential causes of adipose tissue dysfunction, mediated through deficient microfibrils. Circulating asprosin on the other hand is secreted primarily by white adipose tissue under fasting conditions and in obesity. It increases hepatic glucose production and drives insulin secretion and appetite stimulation through inter-organ cross talk. This review discusses the metabolic consequences of fibrillin-1 and fibrillin-1-derived asprosin in pathological conditions. Understanding the dynamic role of fibrillin-1 in the adipose tissue milieu and of circulating asprosin in the body can provide novel mechanistic insights into how fibrillin-1 may contribute to metabolic syndrome. This could lead to new management regimens of patients with metabolic disease.

Transcriptomic analyses suggest that mucopolysaccharidosis patients may be less susceptible to COVID‐19

“…One may predict that all these proteins are required for effective SARS-CoV-2 development; thus, down-regulation of their genes might cause lower susceptibility to COVID-19. The FBN1 gene codes for fibrillin-1, a protein which is proteolytically cleaved to generate an extracellular matrix glycoprotein and asprosin, involved in glucose homeostasis [21]. MFGE8 also codes for a polyprotein which after cleavage is converted into several polypeptides, among which lactahedrin is the major one; lactahedrin is a membrane glycoprotein promoting phagocytosis of apoptotic cells [22].…”

The impaired response of circulating asprosin concentrations to glucose levels fluctuation may be one of the causes of type 2 diabetes – a narrative review

“…Therefore, it appears that the balance between adipokines contributes to the maintenance of homeostasis [7]. In reference, the literature reports that mutations in some of the genes result in increased TGF-β signaling, altered mechanical properties, impaired adipogenesis, leading to adipose tissue dysfunction and giving rise to many conditions, such as Marfan syndrome, marfanoid progeroid lipodystrophy syndrome and neonatal progeroid syndrome [8]. The need to explore this topic led to the discovery of a new adipokine.…”

“…[8]. Single injection of recombinant asprosin leads to immediate increase of both blood glucose and insuline, but all study so far shows that asprosin does not directly affect insulin production in the pancreas [7] [8]. Some reaserches suggested that exercise could also affect the levels of asprosin.…”

“…Moreover, another study reported that the single anaerobic effort induced an increase in asprosin secretion in women. These results indicate that the expression of asprosin in different tissue may be regulated by different factors and different pathways [8] [9].…”

“…It was speculated that the dysregulation of asprosin secretion by white adipose tissue and the impaired response of asprosin to glucose levels fluctuation might be one of the reasons for the onset of type 2 diabetes mellitus and the sustained high level of blood glucose in these patients [2][4] [8].…”