Going Back to the Biology of FGF21: New Insights

Lewis, Jo; Ebling, F. J.; Samms, Ricardo J.; Tsintzas, Kostas

doi:10.1016/j.tem.2019.05.007

Cited by 117 publications

(98 citation statements)

References 119 publications

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“…Interestingly, studies in vitro showed that MCA is significantly involved in neurotoxicity and brain damage primarily by ammonia accumulation, causing perturbation in energy metabolism, increasing lactate, decreasing glutamine concentrations and also inducing apoptosis 31,32 . The observed positive correlation of FGF21 with ammonia and lactate and the negative correlation with glutamine are consistent with these mechanisms, and also indicate the involvement of FGF21 in the regulation of energy metabolism 33 …”

Section: Discussionmentioning

confidence: 71%

Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia

Maines

Catesini

Boenzi

et al. 2020

J of Inher Metab Disea

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Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second-tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long-term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and

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Section: Discussionmentioning

confidence: 71%

Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia

Maines

Catesini

Boenzi

et al. 2020

J of Inher Metab Disea

View full text Add to dashboard Cite

show abstract

“…Consistent with this concept, several studies demonstrated that increases in muscle contraction such as chronic exercise also upregulate muscular FGF21 production [ 50 ]. Now FGF21 has been accepted as an exercise-induced myokine and its circulating level is elevated in response to submaximal exercise [ [51] , [52] , [53] , [54] ], and increased FGF21 secreted from muscle has been regarded as a protective stress response [ 48 , 55 , 56 ]. Recent two studies by employing the skeletal muscle specific FUNDC1-knockout mice or skeletal muscle specific TSC1-knockout mice respectively, demonstrated that muscle-derived FGF21 significantly affected the FGF21 level in serum [ 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

et al. 2020

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Exercise and dietary intervention are currently available strategies to treat nonalcoholic fatty liver disease (NAFLD), while the underlying mechanism remains controversial. Emerging evidence shows that lipophagy is involved in the inhibition of the lipid droplets accumulation. However, it is still unclear if exercise and dietary intervention improve NAFLD through regulating lipophagy, and how exercise of skeletal muscle can modulate lipid metabolism in liver. Moreover, NAFLD is associated with aging, and little is known about the effect of lipid accumulation on aging process. Here in vivo and in vitro models, we found that exercise and dietary intervention reduced lipid droplets formation, decreased hepatic triglyceride in the liver induced by high-fat diet. Exercise and dietary intervention enhanced the lipophagy by activating AMPK/ULK1 and inhibiting Akt/mTOR/ULK1 pathways respectively. Furthermore, exercise stimulated FGF21 production in the muscle, followed by secretion to the circulation to promote the lipophagy in the liver via an AMPK-dependent pathway. Importantly, for the first time, we demonstrated that lipid accumulation exacerbated liver aging, which was ameliorated by exercise and dietary intervention through inducing lipophagy. Our findings suggested a new mechanism of exercise and dietary intervention to improve NAFLD through promoting lipophagy. The study also provided evidence to support that muscle exercise is beneficial to other metabolic organs such as liver. The FGF21-mediated AMPK dependent lipophagy might be a potential drug target for NAFLD and aging caused by lipid metabolic dysfunction.

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“…Recently, growing evidence has supported the key role of adipokines played in the crosstalk between adiposity and decreased insulin sensitivity during pregnancy [23]. As a cytokine, FGF21 was initially isolated from the liver in 2000, and it has since been reported to be widely expressed in metabolic organs such as adipose tissue, pancreas, and the gastrointestinal tract [6]. FGF21 is an important factor in the homeostatic mechanisms with positive effects on glucose and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Fibroblast growth factor 21 (FGF21) is a hormone-like FGF, which is expressed in the liver, adipose tissue, and pancreas [5]. The involvement of FGF21 has been recognized in many metabolic processes such as insulin sensitivity, glucose and lipid metabolism, and energy homeostasis [6,7]. A previous study showed that FGF21 could decrease glucose levels independent of insulin, by improving insulin resistance in peripheral tissues of patients with T2DM [8].…”

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confidence: 99%

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis

et al. 2021

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In recent times, the role of fibroblast growth factor 21 (FGF21) in patients with gestational diabetes mellitus (GDM) has been increasingly investigated. However, to our knowledge, no systematic analysis has been conducted yet to evaluate the relationship between FGF21 levels and GDM. Confirmed studies related to circulating FGF21 levels and GDM were searched from the databases of PubMed, ISI Web of Science, MEDLINE and EMBASE. Data were reported as standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis were performed with Review Manager 5.2 and Stata version 11.0. A total of 392 cases and 435 controls in nine articles were included in this meta-analysis. The circulating FGF21 levels in pregnant women with GDM was higher than that in controls (random effects MD [95% CI] = 0.46, [0.07-0.86], p = 0.02). The result of multivariate meta-regression showed that sample size and point of sample collection contributed to heterogeneity (p = 0.033 and p = 0.047, respectively). Additionally, the results showed that there was no publication bias in this meta-analysis (Z = 1.36, p = 0.175; t = 1.24, p = 0.256, respectively). To conclude, this meta-analysis provides evidence that circulating FGF21 levels are higher in GDM subjects than controls, and it is important to clarify the relationship between circulating FGF21 levels and pregnant women with GDM in accurate prediction of GDM.

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Going Back to the Biology of FGF21: New Insights

Cited by 117 publications

References 119 publications

Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia

Plasma methylcitric acid and its correlations with other disease biomarkers: The impact in the follow up of patients with propionic and methylmalonic acidemia

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis

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