Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers

Rosales‐Soto, Giovanni; Díaz-Vegas, Alexis; Casas, Mariana; Contreras‐Ferrat, Ariel; Jaimovich, Enrique

doi:10.1530/jme-19-0210

Cited by 30 publications

(17 citation statements)

References 68 publications

(88 reference statements)

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“…In skeletal muscle fibers in vitro, low levels of FGF21 induced glucose uptake mediated by the glucose transporter, GLUT4. These data suggest that muscle contractile activity, known to induce FGF21 production, may improve glucose uptake into muscle via FGF21 signaling (Rosales‐Soto et al, 2020; Tezze et al, 2019).…”

Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 96%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 96%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…FGF21 has been proposed as a novel metabolic regulator given its ability to normalize glucose and lipid metabolism and prevent the development of obesity and diabetes [ 125 ]. Recently, it has been reported that FGF21 regulates glucose uptake through a mechanism mediated by GLUT4 and that is dependent on atypical PKC-ζ- in skeletal muscle [ 81 ]. FGF21 gene therapy in animals receiving a long-term high-fat-diet feeding or in ob/ob mice showed marked reductions in body weight, adipose tissue hypertrophy and inflammation, hepatic steatosis inflammation and fibrosis, and insulin resistance due to the higher expression of FGF21 [ 129 ].…”

Section: Myokines Involved In Glucose Uptake In Skeletal Musclementioning

confidence: 99%

Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle

Palomero

2022

Cells

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Insulin resistance onset in skeletal muscle is characterized by the impairment of insulin signaling, which reduces the internalization of glucose, known as glucose uptake, into the cell. Therefore, there is a deficit of intracellular glucose, which is the main source for energy production in the cell. This may compromise cellular viability and functions, leading to pathological dysfunction. Skeletal muscle fibers continuously generate reactive oxygen and nitrogen species (RONS). An excess of RONS produces oxidative distress, which may evoke cellular damage and dysfunction. However, a moderate level of RONS, which is called oxidative eustress, is critical to maintain, modulate and regulate cellular functions through reversible interactions between RONS and the components of cellular signaling pathways that control those functions, such as the facilitation of glucose uptake. The skeletal muscle releases peptides called myokines that may have endocrine and paracrine effects. Some myokines bind to specific receptors in skeletal muscle fibers and might interact with cellular signaling pathways, such as PI3K/Akt and AMPK, and facilitate glucose uptake. In addition, there are cytokines, which are peptides produced by non-skeletal muscle cells, that bind to receptors at the plasma membrane of skeletal muscle cells and interact with the cellular signaling pathways, facilitating glucose uptake. RONS, myokines and cytokines might be acting on the same signaling pathways that facilitate glucose uptake in skeletal muscle. However, the experimental studies are limited and scarce. The aim of this review is to highlight the current knowledge regarding the role of RONS, myokines and cytokines as potential signals that facilitate glucose uptake in skeletal muscle. In addition, we encourage researchers in the field to lead and undertake investigations to uncover the fundamentals of glucose uptake evoked by RONS, myokines, and cytokines.

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“…In skeletal muscle, FGF21 is synthesised under conditions of stress such as mitochondrial myopathies [38]. Studies have demonstrated its ability to increase insulin sensitivity by increasing glucose uptake in primary human skeletal muscle cells and isolated mouse skeletal muscle [57,58] although there is no evidence that this also occurs in vivo [38].…”

Section: Metabolic Functions Of Fgf21mentioning

confidence: 99%

Fibroblast growth factor 21 in heart failure

Tucker

Rye

2022

Heart Fail Rev

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Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF.

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Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers

Cited by 30 publications

References 68 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle

Fibroblast growth factor 21 in heart failure

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