Association between circulating asprosin levels and carotid atherosclerotic plaque in patients with type 2 diabetes
Introduction
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease with an increasing incidence worldwide [1]. With the development of the disease, the risk of microvascular and macrovascular complications in diabetic patients continues to increase [2]. Cardiovascular disease (CVD) is the representative macrovascular complications and the main cause of death in T2DM patients [3]. Therefore, the early prevention and diagnosis of diabetes and its macrovascular complications are particularly important. The occurrence of diabetic cardiovascular disease is a complex process involving multiple factors. Current studies have shown that its main pathophysiological mechanism is atherosclerosis [4], [5]. A large number of data shown that more than 75 % of T2DM patients have vascular atherosclerosis due to hyperglycemia, insulin resistance and hyperlipidemia, which increases the occurrence and development of macrovascular complications [3], [4]. It is generally believed that the pathogenesis of atherosclerosis was multifaceted. More and more studies have found that adipose tissue plays an important role in the occurrence and development of atherosclerosis [6]. In the past, we thought that adipose tissue was just an organ for storing energy. Recently, adipose tissue was supposed to be a major endocrine and paracrine organ, which can produce hundreds of protein molecules called “Adipokines” [7]. As enzymes, hormones, or growth factors, they participate in the regulation of insulin resistance and the metabolism of fat and glucose, and they have an indirect effect on atherosclerosis. In addition, they also directly affect endothelial function, vascular homeostasis and atherosclerosis [8], [9].
Adipokine is a kind of bioactive peptide/protein secreted by adipocytes. It plays a role not only in the energy metabolism, inflammation, and immune response, but also in the process of diabetes and obesity [10], [11], [12], [13]. Adipokines such as leptin, resistin and adiponectin could participate in the occurrence of diabetes and macrovascular complications by regulating insulin signaling and glucolipid metabolism [14], [15]. At present, the role of asprosin in the occurrence and development of diabetes is attracting more and more attention. Asprosin is composed of 140 amino acids. Exon 65 of FBN1 gene encodes 11 amino acids, and exon 66 encodes 129 amino acids, with a size of 30 kDa. Asprosin is a part of profibrillin protein, which is released by the C-terminal of profibrillin protein through specific protein hydrolysis [16], and is mainly expressed in white adipose tissue [16], [17]. Previous studies have found that asprosin was an adipokine very sensitive to energy state. It increased during fasting and decreased when eating [17]. In addition, after entering the circulatory system, asprosin acts on hepatocytes, skeletal muscle and islets, regulates glucose release, insulin secretion and insulin resistance, and finally increases blood glucose [17], [18], [19], [20], [21]. Asprosin can directly activate AgRP neurons through the blood–brain barrier by regulating cAMP-dependent pathway to induce eating and weight gain. It can also inhibit anorexic neuron pro-opiomelanocortin (POMC) and indirectly increase appetite, thus resulting in fat accumulation and weight gain [18], [22]. In conclusion, asprosin has the effect of increasing blood glucose and regulating lipid metabolism. It is closely related to insulin resistance and is an important factor affecting the occurrence and development of diabetic macroangiopathy [23], [24]. However, it is unclear whether circulating asprosin level is associated to the occurrence or development of arterial plaque. In this study, we aimed to explore the relationship between circulating asprosin and carotid plaques in patients with T2DM.
Section snippets
Subjects
The study was approved by the Biomedical Research Ethics Committee of the Affiliated Hospital of Jiangsu University, Jiangsu, China, and performed in accordance with the Declaration of Helsinki. Informed consent was obtained from each participant and all participants were treated in the Department of Endocrinology, Affiliated Hospital of Jiangsu University. A total of 180 T2DM subjects were recruited and completed a standard questionnaire, including lifestyle habits (smoking status, drinking
Clinical and biochemical features in T2DM with carotid plaque group and T2DM without carotid plaque group.
The clinical characteristics of the subgroups studied (T2DM with carotid plaque group and T2DM without carotid plaque group) are shown in Table 1. Compared with T2DM without carotid plaque group, the age, DM duration, SBP, HbA1c, 2hPG, creatinine, hypertension and statin use in T2DM with carotid plaque group were significantly increased (P < 0.05). Most importantly, the level of serum asprosin in T2DM with carotid plaque group was higher than that in T2DM without carotid plaque group
Logistic regression analysis for carotid plaques in T2DM patients
Logistic regression analysis (Table 5 unadjusted) showed that serum asprosin level in type 2 diabetic patients was independently associated with the occurrence of carotid plaques. Moreover, after adjusting different influencing factors, the level of serum asprosin was still closely related to the occurrence of carotid plaque (Table 5 model 1–3).
Discussion
In this study, we provide the evidence for the first time that the levels of serum asprosin were significantly elevated in T2DM patients with carotid plaque, and further ascended in obese patients. The correlation between serum asprosin and carotid plaque in T2DM patients still existed after adjusting for multiple metabolic confounding factors. These results suggested that asprosin may be involved in the occurrence and development of carotid plaque in T2DM patients.
Raised circulating asprosin
Conclusions
In summary, elevated serum asprosin in T2DM patients is a risk factor for carotid plaque, suggesting that asprosin may be involved in the occurrence and development of macrovascular disease in T2DM patients. However, the mechanism of its effect on macrovascular complications of type 2 diabetes needs to be further studied.
Funding
This work was supported by the National Natural Science Foundation of China (81870548), the Social Development Project of Jiangsu Province (BE2018692), the Natural Science Foundation of Jiangsu Province, China (BK20191222), Beigu talent cultivation program of Zhenjiang City, Jiangsu Province.(BGYCB202206), and the Fifth “169 project” Scientific Research Project of Zhenjiang City, Jiangsu Province.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Not applicable.
Author contribution statement
All the authors of this manuscript have made substantial contributions to this work. GY and LY designed the study, drafted the manuscript. XD, ZC and LZ participated in the coordination of the whole work, analyzed data and writing manuscript. CW, DW, and YL interprets the data, revises the manuscript, and recruited participants and collected data. ZC, ZZ, HL, TG, and YX participated in acquisition of data and analyzed the data. All authors read and approved the final manuscript for publication.
Compliance with Ethical Standards
The study was approved by the Biomedical Research Ethics Committee of the Affiliated Hospital of Jiangsu University, Zhenjiang, China, and performed in accordance with the Declaration of Helsinki. All participants had informed consent to the purpose of the study.
Consent for publication
Not applicable.
References (40)
- et al.
IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045
Diabetes Res. Clin. Practice
(2018) - et al.
Prevalence of micro- and macrovascular diabetes complications at time of type 2 diabetes diagnosis and associated clinical characteristics: A cross-sectional baseline study of 6958 patients in the Danish DD2 cohort
J. Diabetes Compl.
(2018) - et al.
Adipokines in health and disease
Trends Pharmacol. Sci.
(2015) - et al.
Adipokines as mediators of endothelial function and atherosclerosis
Atherosclerosis
(2013) - et al.
Adipokines: a link between obesity and cardiovascular disease
J. Cardiol.
(2014) - et al.
Resistin: Potential biomarker and therapeutic target in atherosclerosis
Clin. Chim. Acta
(2021) - et al.
FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders
Gene
(2016) - et al.
Asprosin, a fasting-induced glucogenic protein hormone
Cell
(2016) - et al.
Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation
Mol. Cell. Endocrinol.
(2019) - et al.
A novel biochemical marker for predicting the severity of ACS with unstable angina pectoris: Asprosin
Am. J. Emerg. Med.
(2018)
Asprosin improves the survival of mesenchymal stromal cells in myocardial infarction by inhibiting apoptosis via the activated ERK1/2-SOD2 pathway
Life Sci.
GW29-e0080 The protective role of Asprosin against diabetes in cardiomyocytes
J. Am. Coll. Cardiol.
Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
Lancet Diabetes Endocrinol.
Nationwide study on trends in hospital admissions for major cardiovascular events and procedures among people with and without diabetes in England, 2004–2009
Diabetes Care
Diabetes and atherosclerosis: epidemiology, pathophysiology, and management
JAMA
Atherosclerosis
Circ. Res.
The role of adipose tissue in cardiovascular health and disease, Nature reviews
Cardiology
Relevance of leptin and other adipokines in obesity-associated cardiovascular risk
Nutrients
Adipokines and inflammation: focus on cardiovascular diseases
Int. J. Mol. Sci.
The role of ceramides in diabetes and cardiovascular disease regulation of ceramides by adipokines
Front Endocrinol (Lausanne)
Cited by (6)
Can the new adipokine asprosin be a metabolic troublemaker for cardiovascular diseases? A state-of-the-art review
2023, Progress in Lipid ResearchFibrillin-1 and asprosin, novel players in metabolic syndrome
2023, Molecular Genetics and MetabolismAssociation of serum Asprosin concentrations with heart failure
2023, BMC Cardiovascular DisordersAssociation of serum Asprosin concentrations with heart failure
2023, Research SquareAsprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects
2023, Frontiers in EndocrinologyAdipokines in atherosclerosis: unraveling complex roles
2023, Frontiers in Cardiovascular Medicine
- 1
These authors contributed equally to this work.