Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle

Guo, Ai; Li, Kai; Xiao, Qian

doi:10.1016/j.bbrc.2020.04.002

Cited by 47 publications

(34 citation statements)

References 29 publications

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“…Circulating nutrient excess and particularly the overconsumption of long-chain saturated fatty acids have been reported to trigger metabolic inflammation in a variety of tissues (15)(16)(17)(18)(19), as well as mitochondrial dysfunction marked by mitochondrial fission, decreased oxidative capacity, and increased production of reactive species (8,(20)(21)(22). These effects have been well-described for palmitic acid (PA), with this long-chain saturated fatty acid being reported to induce mitochondrial dysfunction and metabolic inflammation in a variety of tissues both in the central nervous system and the periphery (12,(23)(24)(25)(26)(27). The induction of these pathogenetic mechanisms culminates with the onset of insulin resistance and impaired metabolic health (24,28).…”

Section: Introductionmentioning

confidence: 98%

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

et al. 2021

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The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

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Section: Introductionmentioning

confidence: 98%

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

et al. 2021

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“…PGC‐1α, as a downstream transcription regulator mediated by AMPK and SIRT‐1, is associated with abundant biological pathways in skeletal muscle 26 . Our previous study has suggested that FGF19 can attenuate mitochondrial dysfunction and oxidative stress induced by palmitic acid (PA) through the AMPK/PGC‐1a signalling pathway in C2C12 myotubes 27 . In this study, we further hypothesized that FGF19 could also ameliorate muscle atrophy, lipid and glucose metabolic derangement and abnormal irisin levels via the AMPK/SIRT‐1/PGC‐1α signalling pathway in PA‐treated myotubes and in the skeletal muscle of HFD‐fed mice.…”

Section: Introductionmentioning

confidence: 99%

FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT‐1/PGC‐α pathway

Guo

Tian

et al. 2021

J Cellular Molecular Medi

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Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high‐fat diet (HFD). Increases in muscle atrophy markers (FOXO‐3, Atrogin‐1, MuRF‐1) were abrogated by FGF19 in palmitic acid (PA)‐treated C2C12 myotubes and in the skeletal muscle of HFD‐fed mice. FGF19 not only reduced HFD‐induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC‐1α, UCP‐1, PPAR‐γ) in brown adipose tissue (BAT). FGF19 treatment restored PA‐ and HFD‐induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS‐1, GLUT‐4) and mitigated the PA‐ and HFD‐induced decrease in FNDC‐5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT‐1 and PGC‐1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT‐1/PGC‐α signalling pathway, which might be a potential therapeutic target for obesity and SO.

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“…Mitochondrial biogenesis is modulated by various transcription factors such as peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM). PGC-1α enhances TFAM gene expression by activating nuclear respiratory factor (NRF-1) ( 10 ). High-mobility group box-1 (HMGB1) is a DNA-binding protein that plays a significant role in protecting against mitochondrial abnormalities by modulating heat shock protein beta-1 (HSPB1) gene expression.…”

Section: Tme and Hypoxiamentioning

confidence: 99%

Novel therapies targeting hypoxia mechanism to treat pancreatic cancer

Luo

Qiu

Zheng

et al. 2021

Chinese Journal of Cancer Research

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Pancreatic cancer (PC) is one of the deadliest malignancies. The high mortality rate of PC largely results from delayed diagnosis and early metastasis. Therefore, identifying novel treatment targets for patients with PC is urgently required to improve survival rates. A major barrier to successful treatment of PC is the presence of a hypoxic tumor microenvironment, which is associated with poor prognosis, treatment resistance, increased invasion and metastasis. Recent studies have identified a number of novel molecules and pathways in PC cells that promote cancer cells progression under hypoxic conditions, which may provide new therapy strategies to inhibit the development and metastasis of PC. This review summarizes the latest research of hypoxia in PC and provides an overview of how the current therapies have the capacity to overcome hypoxia and improve PC patient treatment. These findings will eventually provide guidance for future PC management and clinical trials and hopefully improve the survival of patients with PC.

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Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle

Cited by 47 publications

References 29 publications

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT‐1/PGC‐α pathway

Novel therapies targeting hypoxia mechanism to treat pancreatic cancer

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