The relationship of circulating fibroblast growth factor 21 levels with pericardial fat: The Multi-Ethnic Study of Atherosclerosis

Abstract Previous small studies have reported an association between circulating fibroblast growth factor 21 (FGF21) levels and pericardial fat volume in post-menopausal women and high cardiovascular disease (CVD) risk patients. In this study, we investigated the relationship of FGF21 levels with pericardial fat volume in participants free of clinical CVD at baseline. We analysed data from 5765 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) with both pericardial fat volume and plasma FGF21 levels measured at baseline. 4746 participants had pericardial fat volume measured in at least one follow-up exam. After adjusting for confounding factors, ln-transformed FGF21 levels were positively associated with pericardial fat volume at baseline (β = 0.055, p < 0.001). When assessing change in pericardial fat volume over a mean duration of 3.0 years using a linear mixed-effects model, higher baseline FGF21 levels were associated with higher pericardial fat volume at baseline (2.381 cm3 larger in pericardial fat volume per one SD increase in ln-transformed FGF21 levels), but less pericardial fat accumulation over time (0.191 cm3/year lower per one SD increase in ln-transformed FGF21 levels). Cross-sectionally, higher plasma FGF21 levels were significantly associated with higher pericardial fat volume, independent of traditional CVD risk factors and inflammatory markers. However, higher FGF21 levels tended to be associated with less pericardial fat accumulation over time. Nevertheless, such change in pericardial fat volume is very modest and could be due to measurement error. Further studies are needed to elucidate the longitudinal relationship of baseline FGF21 levels with pericardial fat accumulation.

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The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis

Atherosclerosis ◽

10.1016/j.atherosclerosis.2017.12.026 ◽

2018 ◽

Vol 269 ◽

pp. 86-91 ◽

Cited By ~ 5

Author(s):

Tsz Him Hui ◽

Robyn L. McClelland ◽

Matthew A. Allison ◽

Carlos J. Rodriguez ◽

Richard A. Kronmal ◽

...

Keyword(s):

Atrial Fibrillation ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Ethnic Study ◽

Relationship Of ◽

The Relationship

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The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Diabetologia ◽

10.1007/s00125-014-3458-7 ◽

2014 ◽

Vol 58 (3) ◽

pp. 464-473 ◽

Cited By ~ 46

Author(s):

Kwok-Leung Ong ◽

Andrzej S. Januszewski ◽

Rachel O’Connell ◽

Alicia J. Jenkins ◽

Aimin Xu ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Cardiovascular Outcome ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Relationship Of ◽

The Relationship ◽

Fenofibrate Intervention

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Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study

Diabetologia ◽

10.1007/s00125-015-3652-2 ◽

2015 ◽

Vol 58 (9) ◽

pp. 2035-2044 ◽

Cited By ~ 13

Author(s):

Kwok-Leung Ong ◽

◽

Andrzej S. Januszewski ◽

Rachel O’Connell ◽

Luke Buizen ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Microvascular Disease ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Relationship Of ◽

Fenofibrate Intervention

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The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows

BMC Veterinary Research ◽

10.1186/s12917-015-0585-4 ◽

2015 ◽

Vol 11 (1) ◽

Cited By ~ 9

Author(s):

Chuang Xu ◽

Qiushi Xu ◽

Yuanyuan Chen ◽

Wei Yang ◽

Cheng Xia ◽

...

Keyword(s):

Growth Factor ◽

Energy Balance ◽

Dairy Cows ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Characteristic Parameters ◽

The Relationship

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Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice

Scientific Reports ◽

10.1038/srep30484 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 31

Author(s):

Fenni Rusli ◽

Joris Deelen ◽

Evi Andriyani ◽

Mark V. Boekschoten ◽

Carolien Lute ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Liver Fat ◽

Signalling Pathways ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Fat Accumulation

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Fibroblast growth factor 21 (FGF21) is increased in MDD and interacts with body mass index (BMI) to affect depression trajectory

Translational Psychiatry ◽

10.1038/s41398-021-01679-y ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Brittany L. Mason ◽

Abu Minhajuddin ◽

Andrew H. Czysz ◽

Manish K. Jha ◽

Bharathi S. Gadad ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Early Onset ◽

Clinical Care ◽

Fibroblast Growth Factor 21 ◽

Healthy Controls ◽

Fibroblast Growth ◽

Depression Severity ◽

Major Depressive ◽

Over Time

AbstractFibroblast growth factor 21 (FGF21) is a key regulator of metabolic function and nutrient preference. It also affects biological pathways associated with major depressive disorder (MDD), including corticotrophin-releasing hormone (CRH), leptin, and sympathetic activity. Lower levels of cerebrospinal fluid FGF21 have been associated with higher Beck Depression Inventory scores. FGF21 was examined as a metabolic marker that could be associated with MDD and evaluated as a biomarker of antidepressant treatment response in a large, randomized placebo-controlled trial in chronic, early-onset MDD participants. FGF21 levels at baseline and during treatment were determined for participants in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. FGF21 was analyzed by ELISA in individuals with chronic, early-onset MDD (first major depressive episode before 30 years) compared to healthy control participants. Participants with MDD had higher levels of FGF21 compared to healthy controls (HCs), even after controlling for baseline age, sex, race, Hispanic ethnicity, BMI, and site (β-coefficient = 1.20, p < 0.0001, Cohen’s d = 0.60). FGF21 did not change over time nor differ between treatment groups. Interestingly though, those with normal BMI and lower FGF21 levels showed a reduction in depression severity over time compared to all other groups. In conclusion, depression is associated with higher levels of FGF21 compared to healthy controls and those with lower levels of FGF21 (25th percentile of the sample) in the context of normal-weight BMI seem to have improved depression severity over time.

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The relationship of fibroblast growth factors 21 and 23 and α-Klotho with platelet activity measured by platelet volume indices

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1251 ◽

2015 ◽

Vol 53 (10) ◽

Cited By ~ 2

Author(s):

Yoshihiro Takeda ◽

Shu-ichi Fujita ◽

Toshiyuki Ikemoto ◽

Yoshikatsu Okada ◽

Koichi Sohmiya ◽

...

Keyword(s):

Linear Regression Analysis ◽

Positive Association ◽

Lipid Lowering ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Platelet Activity ◽

Platelet Volume ◽

Distribution Width ◽

Relationship Of ◽

The Relationship

AbstractSubjects with high fibroblast growth factor 21(FGF21) and 23 (FGF23), endocrine hormones that regulate insulin sensitivity and phosphate metabolism, respectively, are reported to have a higher risk for adverse cardiovascular outcome. Therefore, the relationship of FGF21, FGF23, and α-Klotho (co-receptor for FGF23 signaling) with mean platelet volume (MPV) and platelet distribution width (PDW), two platelet volume indices that reflect platelet activity, was investigated.Data from 156 patients admitted to the cardiology department were analyzed. MPV and PDW were measured by an automatic blood counter, and serum FGF21, FGF23, and α-Klotho concentrations were measured by an enzyme-linked immunoassay.Log(FGF21) was significantly correlated with serum triglycerides but did not differ according to the use of non-use of antidiabetic or lipid-lowering drugs. MPV and PDW were significantly correlated (R=0.475, p<0.001). MPV was significantly correlated with log(FGF21) (R=–0.167, p<0.05) and log(FGF23) (R=0.351, p<0.001) but not with log(α-Klotho). Linear regression analysis showed a negative and positive association of log(FGF21) and log(FGF23), respectively, with MPV that was independent of possible confounders including sex, age, renal function, and antithrombotic drug use. In addition, log(FGF23) was found to have a significant independent positive association with PDW.Among cardiac patients, FGF21 had a negative association with MPV, whereas FGF23 had a positive association. Future studies of serum FGF23/FGF21 concentrations and the incidence of thromboembolic disorders are warranted.

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Sex Modifies the Association of Fibroblast Growth Factor 21 With Subclinical Carotid Atherosclerosis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.627691 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yingjie Chee ◽

Grace Lx Toh ◽

Chien Joo Lim ◽

Liuh Ling Goh ◽

Rinkoo Dalan

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Carotid Atherosclerosis ◽

Subclinical Atherosclerosis ◽

Density Lipoprotein ◽

Population Based ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

The Relationship ◽

Interaction Test

Background and Aims: Fibroblast growth factor 21 (FGF21), an emerging metabolic hepatokine, is associated with atherosclerosis. An interaction with sex has been described in various populations. We aimed to study whether sex modulates the relationship between FGF21 and subclinical carotid atherosclerosis in a diabetes-enriched multiethnic population of Singapore. We explore differences in intermediary mechanisms, in terms of hypertension, lipids, and inflammation, between FGF21 and atherosclerosis.Methods: We recruited 425 individuals from a single diabetes center in Singapore, and demographics, anthropometry, metabolic profile, FGF21, and carotid ultrasonography were performed. Multivariable logistic regression models were used to study the association between subclinical atherosclerosis and FGF21 adjusting for age, ethnicity, body mass index (BMI), hemoglobin A1c (HbA1c), systolic and diastolic blood pressures, and low-density lipoprotein (LDL)-cholesterol separately for males and females as two groups after an interaction test.Results: An interaction test assessing interaction by sex on the relationship between subclinical atherosclerosis and FGF21 showed a significant interaction with sex (Pinteraction = 0.033). In the female subgroup, significant independent associations of standardized lnFGF21 with subclinical atherosclerosis were seen, with 1 SD increment in lnFGF21 being associated with 1.48-fold (95% CI: 1.03, 2.12; p = 0.036) increase in risk. In the male subgroup, the association of subclinical atherosclerosis with standardized lnFGF21 was not significant [odds ratio (OR) (95% CI): 0.90 (0.63, 1.28); p = 0.553]. We found sex interactions with pulse pressure being significantly associated in females only and triglycerides and C-reactive protein being associated with males only.Conclusion: FGF21 is positively associated with subclinical carotid atherosclerosis in women, but not in men. The sex–racial patterns in the mechanisms by which FGF21 causes subclinical atherosclerosis needs to be explored in larger population-based studies and mechanistically studied in greater detail.

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