Fibroblast growth factor 21 in non-alcoholic fatty liver disease

Tucker, Bradley; Li, Huating; Long, Xiaoxue; Rye, Kerry‐Anne; Ong, Kwok Leung

doi:10.1016/j.metabol.2019.153994

Cited by 106 publications

(93 citation statements)

References 117 publications

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“…Although the underlying mechanism for the development and progression of NAFLD is complex and multifactorial, obesity and insulin resistance are thought to be key pathogenic factors, as they lead to exacerbated lipolysis in adipose tissues, with consequent increased flux of free fatty acids (FFAs) to the liver (Samuel & Shulman, 2018; Tucker, Li, Long, Rye, & Ong, 2019). The oversupply of plasma FFAs to the liver leads to hepatic lipid accumulation, insulin resistance, glycogen reduction, and steatohepatitis with mitochondrial dysfunction, endoplasmic reticulum stress, and the release of reactive oxygen species (Buzzetti et al., 2016; Leamy, Egnatchik, & Young, 2013).…”

Section: Resultsmentioning

confidence: 99%

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Gai

Zhou

Zhang

et al. 2020

Journal of Food Science

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Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)‐induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 µM CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element‐binding protein‐1, fatty acid synthase, and stearoyl‐CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3β while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP‐activated protein kinase (AMPK) inhibitor and small interfering RNA‐liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA‐induced HepG2 cells via the LKB1/AMPK signaling pathway. Practical Application In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathway in vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.

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Section: Resultsmentioning

confidence: 99%

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Gai

Zhou

Zhang

et al. 2020

Journal of Food Science

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“…FGF21 can reduce glucose levels without triggering hypoglycemia, and increase the glucose uptake in brown fat, the browning of white fat and the increase in overall energy consumption. As a metabolic regulator, FGF21 significantly reduces the expression of key genes involved in lipid metabolism, including stearoyl-coenzyme A desaturase 1 and glucokinase, reduces fat syntheses, upregulates the expression of key genes involved in lipolysis, including leptin receptor and insulin-like growth factor binding protein 2 and promotes fat decomposition and energy metabolism, thereby reducing the accumulation of fat in liver tissue and restoring normal liver function (40).…”

Section: Glucose Metabolism In Nafldmentioning

confidence: 99%

Abnormal metabolic processes involved in the pathogenesis of non‑alcoholic fatty liver disease (Review)

Shao

Qin

et al. 2020

Exp Ther Med

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and can lead to liver cirrhosis or liver cancer in severe cases. In recent years, the incidence of NAFLD has increased substantially. The trend has continued to increase and has become a key point of concern for health systems. NAFLD is often associated with metabolic abnormalities caused by increased visceral obesity, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, atherosclerosis and systemic microinflammation. Therefore, the pathophysiological mechanisms of NAFLD must be clarified to develop new drug treatment strategies. Recently, researchers have conducted numerous studies on the pathogenesis of NAFLD and have identified various important regulatory factors and potential molecular mechanisms, providing new targets and a theoretical basis for the treatment of NAFLD. However, the pathogenesis of NAFLD is extremely complex and involves the interrelationship and influence of multiple organs and systems. Therefore, the condition must be explored further. In the present review, the abnormal metabolic process, including glucose, lipid, amino acid, bile acid and iron metabolism are reviewed. It was concluded that NAFLD is associated with an imbalanced metabolic network that involves glucose, lipids, amino acids, bile acids and iron, and lipid metabolism is the core metabolic process. The current study aimed to provide evidence and hypotheses for research and clinical treatment of NAFLD.

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“…Mechanistically, the elevation of circulating FGF21 levels might result from dysfunctional peroxisome proliferatoractivated receptor-α signaling, which provided the potential mechanism for the association of FGF23 and NAFLD. 32 There were some limitations to the present study. Firstly, because of the cross-sectional nature of the present study, the chronological and causal sequences of changes in the serum FGF23 levels and the occurrence and development of hepatic steatosis were hard to determine.…”

Section: Discussionmentioning

confidence: 86%

<p>Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes</p>

Hu¹,

Yang²,

Wang³

et al. 2020

DMSO

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Purpose: Fibroblast growth factor (FGF) 23 is currently recognized to be involved in the occurrence and development of metabolic diseases. The present study aimed to investigate the association between serum FGF23 levels and hepatic steatosis, as well as the influence of sleep duration. Patients and Methods: The present study population was selected from patients with diagnosed diabetes hospitalized during February 2018 to April 2019. Serum FGF23 levels were assessed by two-side sandwich enzyme-linked immunosorbent assay. The presence and severity of hepatic steatosis were determined by controlled attenuation parameter (CAP). Hepatic steatosis was determined as CAP≥302 dB/m. Results: Serum FGF23 levels were significantly higher in individuals with hepatic steatosis than in those without hepatic steatosis (P=0.004). The present study population was divided into Q1-Q4 according to serum FGF23 quartiles. The risks of hepatic steatosis were increased more than 3 folds in Q2-Q4 (all P<0.01) compared to Q1. CAP showed an uptrend from Q1 to Q4 (P=0.005), even after adjustment for gender and age (P=0.001). Multivariate variance analyses showed significant differences in CAP among Q1-Q4 (P=0.008) and between individuals with short and long sleep duration (P=0.023), which were independent of each other. Serum FGF23 levels were positively associated with CAP independent of gender, age, total metabolic traits, and sleep duration (P=0.042). Conclusion: Serum FGF23 levels were independently and positively associated with the severity of hepatic steatosis. The associations of serum FGF23 levels and sleep duration with hepatic steatosis were independent of each other.

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Fibroblast growth factor 21 in non-alcoholic fatty liver disease

Cited by 106 publications

References 117 publications

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Abnormal metabolic processes involved in the pathogenesis of non‑alcoholic fatty liver disease (Review)

<p>Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes</p>

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