scholarly journals Increased plasma FGF21 level as an early biomarker for insulin resistance and metabolic disturbance in obese insulin-resistant rats

2018 ◽  
Vol 15 (3) ◽  
pp. 263-269 ◽  
Author(s):  
Pongpan Tanajak ◽  
Wanpitak Pongkan ◽  
Siriporn C Chattipakorn ◽  
Nipon Chattipakorn

Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet–induced obese rats. Methods: In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways. Results: Body weight and plasma fibroblast growth factor 21 levels were increased after 4 weeks of consumption of a high-fat diet. At weeks 8 and 12, high-fat diet rats had significantly increased body weight and plasma fibroblast growth factor 21 levels, together with increased plasma insulin, HOMA index, area under the curve of glucose, plasma total cholesterol, plasma low-density lipoprotein cholesterol, serum malondialdehyde and cardiac malondialdehyde levels. However, plasma high-density lipoprotein cholesterol levels and cardiac fibroblast growth factor 21 signalling proteins (p-FGFR1 Tyr154, p-ERK1/2 Thr202/Tyr204 and p-Akt Ser473) were decreased, compared with normal diet rats. Conclusion: These findings suggest that plasma fibroblast growth factor 21 levels could be an early predictive biomarker prior to the development of insulin resistance, metabolic disturbance and cardiac fibroblast growth factor 21 resistance.

Abstract Background and aims The prevalence of non-alcoholic fatty liver disease has been alarmingly increased with no lines of effective treatment. Vanillic acid is a naturally occurring polyphenol with promising therapeutic effects. Exercise is well known to be an effective tool against obesity and its consequences. Thus, we aim to study the effect of vanillic acid alone and along with exercise on fatty liver induced by a high-fat diet in a rat model and to investigate possible novel mechanisms involved in their action. Methods In this study, 40 male rats were divided equally into five groups: control (standard chow diet), HFD (high-fat diet), HFD+VA (HFD+ vanillic acid (50 mg/kg/day orally), HFD+EX (HFD+ swimming exercise 5 days/week), HFD+VA+EX (HFD+ vanillic acid+ swimming exercise) for eight weeks. Results Body mass, liver weight, liver enzymes, cholesterol, and triglycerides were significantly decreased in the combined VA+EX group, with marked improvement in hyperglycemia, hyperinsulinemia, and consequently HOMA-IR index compared to the HFD group. These improvements were also reflected in the pathological view. VA and swimming, either solely or in combination, markedly increased hepatic and circulating fibroblast growth factor 21. Additionally, VA and swimming increased the immunohistochemical expression of the autophagosomal marker LC3 and decreased the expression of P62, which is selectively degraded during autophagy. Conclusions These results suggest the hepatoprotective effect of VA and swimming exercise against fatty liver and the involvement of FGF21 and autophagy in their effect.


PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148252 ◽  
Author(s):  
Garima Singhal ◽  
ffolliott Martin Fisher ◽  
Melissa J. Chee ◽  
Tze Guan Tan ◽  
Abdelfattah El Ouaamari ◽  
...  

Cytokine ◽  
2012 ◽  
Vol 59 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Bin Sun ◽  
Gangyi Yang ◽  
Mengliu Yang ◽  
Hua Liu ◽  
Guenther Boden ◽  
...  

2019 ◽  
Vol 3 (4) ◽  
pp. 825-837 ◽  
Author(s):  
Satu Seppä ◽  
Sirpa Tenhola ◽  
Raimo Voutilainen

Abstract Context Among cytokines, fibroblast growth factor 21 (FGF21), adiponectin (Adn), and irisin have been considered potential biomarkers for insulin sensitivity (IS). Objective We evaluated whether serum FGF21, Adn, and irisin associate with markers of IS and serum lipids in 12-year-old children. Design, Participants, and Main Outcome Measures This cohort study included 192 12-year-old children (109 girls). Seventy-eight of them had been born appropriate for gestational age (AGA), 70 small for gestational age (SGA), and 44 from preeclamptic pregnancies (PREs) as AGA. Fasting serum FGF21, Adn, irisin, lipids, inflammatory markers, and IS markers were measured. Quantitative insulin sensitivity check index (QUICKI) was calculated. Results The means of serum FGF21, high molecular weight (HMW) Adn, and irisin did not differ between the sexes or between the SGA, AGA, and PRE children. In the whole study population, FGF21 associated positively with irisin and uric acid and negatively with leptin and high-density lipoprotein cholesterol (HDL-C). HMW Adn associated positively with total Adn, HDL-C, leptin, and SHBG. Apart from FGF21, irisin associated positively with insulin, high-sensitivity C-reactive protein, γ-glutamyltransferase, and triglycerides, and negatively with QUICKI, SHBG, and IGF binding protein-1. In multivariate regression analyses, irisin predicted lower IS and HMW Adn predicted higher HDL-C body mass index-independently, whereas FGF21 had no independent contribution to IS or lipid variables. Conclusion In 12-year-old children, serum irisin was associated with markers reflecting reduced IS. HMW Adn predicted HDL-C, whereas FGF21 did not contribute to IS or lipid parameters in multivariate regression analyses.


2020 ◽  
Vol 21 (18) ◽  
pp. 6836
Author(s):  
Hyo Jin Maeng ◽  
Gha Young Lee ◽  
Jae Hyun Bae ◽  
Soo Lim

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE−/− mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.


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