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      Characterization of fibroblast growth factor 1 in obese children and adolescents

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          Abstract

          Background

          Fibroblast growth factor 1 (FGF1) can regulate glucose and lipid metabolism in obese mice. Serum FGF1 has increased in type 2 diabetes mellitus adults and correlated with BMI. This study aimed to indicate conventional weight loss effects on FGF1 in obese children and adolescents.

          Materials and methods

          Clinical and metabolic parameters of 88 lean and obese individuals (ages 5–15 years) and 39 obese individuals followed with 6 months of lifestyle intervention were collected. Serum FGF1 levels were detected through enzyme-linked immunosorbent assays.

          Results

          FGF1 levels were increased in obese individuals. Serum FGF1 levels were significantly correlated with BMI and waist circumferences ( r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise linear regression analyses showed that FGF1 levels were significantly correlated with HbA1c and HOMA-IR ( β = 0.371, P = 0.008; β = 0.323, P = 0.021, respectively). Weight loss (2.3 ± 0.1 kg) was accompanied by a significant reduction of circulating FGF1 levels (7.2 ± 0.4 pg/mL). Changes in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR and low-density lipoprotein cholesterol ( β = 0.277, P = 0.020; β = 0.474, P < 0.001; β = 0.320, P = 0.008, respectively).

          Conclusion

          FGF1 was related to increased risk of insulin resistance in obese children and adolescents. Serum FGF1 reduced after weight loss in obese individuals and was associated with the improvement of insulin resistance. Changes in serum FGF1 were more correlated with insulin resistance than changes in obesity per se.

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          Most cited references18

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          Pediatric Obesity—Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline

          The European Society of Endocrinology and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society.
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            Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.

            Hormonal control of metabolic rate can be important in regulating the imbalance between energy intake and expenditure that underlies the development of obesity. In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05 liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant change in food intake. Furthermore, in addition to a reduction in weight gain, treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin. To explore the mechanisms underlying the FGF19-mediated increase in metabolic rate, we profiled the FGF19-induced gene expression changes in the liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a gene expression profile that is consistent with activation of this tissue. We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent with the experimentally determined increase in fat oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation.
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              FGF19, FGF21, and an FGFR1/β-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia.

              Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor β-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects. In contrast, β-Klotho in neurons is essential for both FGF19 and FGF21 to cause weight loss and lower glucose and insulin levels. We further show an FGF21 mimetic antibody that activates the FGF receptor 1/β-Klotho complex also requires neuronal β-Klotho for its metabolic effects. These studies highlight the importance of the nervous system in mediating the beneficial weight loss and glycemic effects of endocrine FGF drugs.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                August 2018
                09 July 2018
                : 7
                : 8
                : 932-940
                Affiliations
                [1 ]Department of Pediatrics Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
                [2 ]Department of Pediatrics The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
                [3 ]Department of Pediatrics Boai Hospital of Zhongshan, Zhongshan, China
                Author notes
                Correspondence should be addressed to X Luo: xpluo@ 123456tjh.tjmu.edu.cn
                Article
                EC180141
                10.1530/EC-18-0141
                6130312
                29991637
                16e19e60-e83d-4f40-8da9-3d3ed713abfd
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 03 July 2018
                : 09 July 2018
                Categories
                Research

                fibroblast growth factor 1,weight loss,children and adolescents,obesity

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