Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease

Shen, Yun; Ma, Xiaojing; Zhou, Jian; Pan, Xiaoping; Hao, Yaping; Zhou, Mi; Lu, Zhigang; Gao, Mingyu; Bao, Yuqian; Jia, Weiping

doi:10.1186/1475-2840-12-124

Cited by 129 publications

(110 citation statements)

References 22 publications

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“…Our findings have expanded the current understanding on the relationship between serum FGF21 and CHD. Several cross‐sectional studies had shown that serum FGF21 levels were significantly higher in subjects with CHD than those in controls 13, 14. In a study involving 100 Chinese subjects, with 38% of them having T2DM, serum FGF21 levels were independently associated with the presence of acute myocardial infarction and were significantly higher in those who developed reinfarction within 30 days 15.…”

Section: Discussionmentioning

confidence: 99%

“…Over the years, the association of circulating FGF21 with CHD in T2DM has not been clearly defined. In cross‐sectional studies, conflicting results were reported regarding circulating FGF21 levels in subjects with CHD, with an association of raised FGF21 levels with CHD reported in some studies,13, 14, 15 but not in others 16, 17. The association of circulating FGF21 with CHD in T2DM, especially among those without known cardiovascular disease (CVD), remains to be defined.…”

Section: Introductionmentioning

confidence: 99%

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Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Lee

Woo

Chow

et al. 2017

JAHA

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BackgroundFibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross‐sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases.Methods and ResultsBaseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow‐up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow‐up of 4 years. Baseline serum log‐transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8–438.4] versus 151.1 pg/mL [75.6–274.6]; P<0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10–2.19; P=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors.ConclusionsWe have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Lee

Woo

Chow

et al. 2017

JAHA

View full text Add to dashboard Cite

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“…Available data on gender differences in FGF-21 concentration in non-diabetic population vary widely: from equal FGF-21 concentration [24,25] to lower [21] and higher FGF-21 concentration in women [26,27].…”

mentioning

confidence: 99%

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

et al. 2014

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“…FGF21 currently receives general interest as one of the most promising clinical anti-diabetic drug candidate [4], but, paradoxically, circulating endogenous FGF21 is elevated during obesity [48,49], type 2 diabetes [50], and coronary artery disease [51]. In contrast, its induction and secretion from skeletal muscle in response to mitochondrial perturbations and ISR activation [8e11] raised the idea of an adaptive mitochondrial stress-related pseudo-starvation response via endogenous FGF21.…”

Section: Discussionmentioning

confidence: 99%

Muscle mitochondrial stress adaptation operates independently of endogenous FGF21 action

et al. 2016

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Objective: Fibroblast growth factor 21 (FGF21) was recently discovered as stress-induced myokine during mitochondrial disease and proposed as key metabolic mediator of the integrated stress response (ISR) presumably causing systemic metabolic improvements. Curiously, the precise cell-non-autonomous and cell-autonomous relevance of endogenous FGF21 action remained poorly understood. Methods: We made use of the established UCP1 transgenic (TG) mouse, a model of metabolic perturbations made by a specific decrease in muscle mitochondrial efficiency through increased respiratory uncoupling and robust metabolic adaptation and muscle ISR-driven FGF21 induction. In a cross of TG with Fgf21-knockout (FGF21 À/À ) mice, we determined the functional role of FGF21 as a muscle stress-induced myokine under low and high fat feeding conditions. Results: Here we uncovered that FGF21 signaling is dispensable for metabolic improvements evoked by compromised mitochondrial function in skeletal muscle. Strikingly, genetic ablation of FGF21 fully counteracted the cell-non-autonomous metabolic remodeling and browning of subcutaneous white adipose tissue (WAT), together with the reduction of circulating triglycerides and cholesterol. Brown adipose tissue activity was similar in all groups. Remarkably, we found that FGF21 played a negligible role in muscle mitochondrial stress-related improved obesity resistance, glycemic control and hepatic lipid homeostasis. Furthermore, the protective cell-autonomous muscle mitohormesis and metabolic stress adaptation, including an increased muscle proteostasis via mitochondrial unfolded protein response (UPR mt ) and amino acid biosynthetic pathways did not require the presence of FGF21.Conclusions: Here we demonstrate that although FGF21 drives WAT remodeling, the adaptive pseudo-starvation response under elevated muscle mitochondrial stress conditions operates independently of both WAT browning and FGF21 action. Thus, our findings challenge FGF21 as key metabolic mediator of the mitochondrial stress adaptation and powerful therapeutic target during muscle mitochondrial disease.

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Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease

Cited by 129 publications

References 22 publications

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

Muscle mitochondrial stress adaptation operates independently of endogenous FGF21 action

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