High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state

Lee, Sun Young; Kim, Deog-Yoon; Kwak, Mi Kyung; Ahn, Seong Hee; Kim, Hyeonmok; Kim, Beom Jun; Koh, Jung Min; Rhee, Yumie; Kim, Chong Hwa; Baek, Ki Hyun; Min, Yong Ki; Lee, Seung Hun; Kang, Moo Il

doi:10.1507/endocrj.ej18-0352

Cited by 13 publications

(13 citation statements)

References 33 publications

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“…Moreover, one study reported the positive correlation between FSTL 1 levels and BMI, 2) but another did not. 17) We found no correlation between FSTL1 levels and BMI. In this present study, we demonstrated that FSTL1 levels were a significant factor associated with CAD independent of hsCRP and creatinine levels and BMI.…”

Section: Discussioncontrasting

confidence: 53%

“…10) The production of FSTL1 in infarcted myocardium was reported in patients with acute MI, 16) but no significant difference was noted in terms of the serum FSTL1 levels among 62 patients with unstable angina, 68 with non-ST-elevation MI, and 86 with ST-elevation MI. 10) Regarding the associations between blood FSTL1 levels and stable CAD or coronary atherosclerosis, only one small study 17) reported that serum FSTL1 levels tended to be higher in 28 subjects with coronary artery plaque detected by computed tomography than in 38 without plaque, but this difference did not reach statistical significance, probably due to the small number of study subjects. We then investigated the plasma FSTL1 levels in 350 patients who underwent elective coronary angiography.…”

Section: Discussionmentioning

confidence: 99%

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Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease

et al. 2021

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Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein known for its role in inflammation. However, plasma FSTL1 levels in patients with coronary artery disease (CAD) have not been fully elucidated. Thus, in this study, we investigated the plasma FSTL1 levels of 350 patients who underwent elective coronary angiography. The severity of CAD was represented as the numbers of > 50% stenotic vessels and segments and the severity score. CAD was detected in 196 patients, of whom 84 had 1-vessel disease (1-VD), 62 had 2-VD, and 50 had 3-VD. Plasma high-sensitivity C-reactive protein (hsCRP) levels were higher in patients with CAD than in those without CAD (median 0.56 versus 0.44 mg/L, P < 0.01). Notably, plasma FSTL1 levels were higher in patients with CAD than in those without CAD (median 4.05 versus 3.47 ng/mL, P < 0.02). A stepwise increase in FSTL1 levels was found depending on the number of > 50% stenotic vessels: 3.47 in CAD(−), 3.74 in 1-VD, 4.42 in 2-VD, and 4.65 ng/mL in 3-VD (P < 0.05). FSTL1 levels also correlated with the number of > 50% stenotic segments and the severity score (r = 0.14 and r = 0.15, respectively, P < 0.005) and hsCRP levels (r = 0.10, P < 0.05). In the multivariate analysis, FSTL1 levels were an independent factor associated with CAD. The odds ratio for CAD was 1.61 (95% CI = 1.01-2.58) for high FSTL1 level of > 3.6 ng/mL (P < 0.05). In conclusion, plasma FSTL1 levels in patients with CAD were found to be high and associated with the presence and severity of CAD, thus, suggesting that FSTL1 may play a role in the progression of coronary atherosclerosis.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease

et al. 2021

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“…Because obesity is characterized by excessive accumulation of white adipose tissue, targeting adipogenesis represents a promising strategy to manage obesity [ 34 ]. Serum levels of FSTL1 were found to be higher in overweight and obese subjects than in controls, which indicates a potential pro-obesity effect [ 35 , 36 ]. The specific role and molecular mechanism of FSTL1 in adipogenesis have not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Fang

Jia

et al. 2022

Molecular Metabolism

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Objective Although Follistatin-like protein 1 (FSTL1), as an “adipokine”, is highly expressed in preadipocytes, the detail role of FSTL1 in adipogenesis and obesity remains not fully understood. Methods In vitro differentiation of both Fstl1 −/− murine embryonic fibroblasts (MEFs) and stromal vascular fraction (SVF) were measured to assess the specific role of FSTL1 in adipose differentiation. Fstl1 adipocyte-specific knockout mice were generated to evaluate its role in obesity development. Gene expression analysis and phosphorylation patterns were performed to check out the molecular mechanism of the biological function of FSTL1. Results FSTL1 deficiency inhibited preadipocytes differentiation in vitro and obesity development in vivo. Glycosylation at N142 site was pivotal for the biological effect of FSTL1 during adipogenesis; the conversion between PPARγ and p-PPARγ was the key factor for the function of FSTL1. Molecular mechanism studies showed that FSTL1 functions through the integrin/FAK/ERK signaling pathway. Conclusions Our results suggest that FSTL1 promotes adipogenesis by inhibiting the conversion of PPARγ to p-PPARγ through the integrin/FAK/ERK signaling pathway. Glycosylated modification at N142 of FSTL1 is the key site to exert its biological effect.

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“…Martin Horak et al showed in their study that overweight and moderate obesity are associated with increased levels of FSTL1 primarily due to its pro-inflammatory action during chronic mildly inflammatory condition [102]. On the other hand, pathological and severe obesity decreased FSTL1 levels due to a continuous increase in the number of matured adipocytes and other associated factors [102][103][104]. In addition, the secretion of FSTL1 may be regulated by hyperinsulinemia and free fatty acids [105][106][107].…”

Section: Pathologies Of Osteo-and Myohistogenesismentioning

confidence: 99%

Follistatin-Like Proteins: Structure, Functions and Biomedical Importance

2021

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Main forms of cellular signal transmission are known to be autocrine and paracrine signaling. Several cells secrete messengers called autocrine or paracrine agents that can bind the corresponding receptors on the surface of the cells themselves or their microenvironment. Follistatin and follistatin-like proteins can be called one of the most important bifunctional messengers capable of displaying both autocrine and paracrine activity. Whilst they are not as diverse as protein hormones or protein kinases, there are only five types of proteins. However, unlike protein kinases, there are no minor proteins among them; each follistatin-like protein performs an important physiological function. These proteins are involved in a variety of signaling pathways and biological processes, having the ability to bind to receptors such as DIP2A, TLR4, BMP and some others. The activation or experimentally induced knockout of the protein-coding genes often leads to fatal consequences for individual cells and the whole body as follistatin-like proteins indirectly regulate the cell cycle, tissue differentiation, metabolic pathways, and participate in the transmission chains of the pro-inflammatory intracellular signal. Abnormal course of these processes can cause the development of oncology or apoptosis, programmed cell death. There is still no comprehensive understanding of the spectrum of mechanisms of action of follistatin-like proteins, so the systematization and study of their cellular functions and regulation is an important direction of modern molecular and cell biology. Therefore, this review focuses on follistatin-related proteins that affect multiple targets and have direct or indirect effects on cellular signaling pathways, as well as to characterize the directions of their practical application in the field of biomedicine.

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High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state

Cited by 13 publications

References 33 publications

Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease

Association between Plasma Follistatin-like Protein 1 Levels and the Presence and Severity of Coronary Artery Disease

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis

Follistatin-Like Proteins: Structure, Functions and Biomedical Importance

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