FGF19 and FGF21 serum concentrations in human obesity and type 2 diabetes behave differently after diet- or surgically-induced weight loss

Gómez-Ambrosi, Javier; Gallego-Escuredo, José M.; Catalán, Victoria; Rodríguez, Amaia; Domingo, Peré; Moncada, Rafael; Valentí, Víctor; Salvador, Javier; Giralt, Marta; Villarroya, Francesc; Frühbeck, Gema

doi:10.1016/j.clnu.2016.04.027

Cited by 138 publications

(121 citation statements)

References 41 publications

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“…Circulating levels of FGF21 have been shown to be increased in obesity being further increased in obesity‐associated T2D and also correlated with the glycaemic level . Importantly, FGF21 levels were reduced after diet‐ or surgically induced weight loss …”

Section: Adipose Tissue Inflammation and Dysregulated Adipokine Profimentioning

confidence: 98%

“…130 Circulating levels of FGF21 have been shown to be increased in obesity being further increased in obesity-associated T2D and also correlated with the glycaemic level. 131,132 Importantly, FGF21 levels were reduced after diet-or surgically induced weight loss. 132 Interleukin-32 (IL-32), also termed as TNF-α-inducing factor and natural killer cell transcript (NK)-4, is a recently described cytokine produced by immune and nonimmune cells including natural killer cells, monocytes, macrophages, T lymphocytes, fibroblasts as well as epithelial and endothelial cells.…”

Section: F I G U R Ementioning

confidence: 99%

“…131,132 Importantly, FGF21 levels were reduced after diet-or surgically induced weight loss. 132 Interleukin-32 (IL-32), also termed as TNF-α-inducing factor and natural killer cell transcript (NK)-4, is a recently described cytokine produced by immune and nonimmune cells including natural killer cells, monocytes, macrophages, T lymphocytes, fibroblasts as well as epithelial and endothelial cells. 133,134 IL-32 exerts important roles in the pathogenesis of infectious, autoimmune and inflammatory diseases.…”

Section: F I G U R Ementioning

confidence: 99%

“…A recent study has reported that ob/ob and diet‐induced obese mice exhibited elevated circulating levels of FGF21, being also less sensitive to exogenous FGF21 administration . Circulating levels of FGF21 have been shown to be increased in obesity being further increased in obesity‐associated T2D and also correlated with the glycaemic level . Importantly, FGF21 levels were reduced after diet‐ or surgically induced weight loss …”

Section: Adipose Tissue Inflammation and Dysregulated Adipokine Profimentioning

confidence: 99%

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Adipokine dysregulation and adipose tissue inflammation in human obesity

Unamuno

Gómez-Ambrosi

Rodrı́guez

et al. 2018

Eur J Clin Investigation

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478

331

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Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.

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Section: Adipose Tissue Inflammation and Dysregulated Adipokine Profimentioning

confidence: 98%

Section: F I G U R Ementioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

Section: Adipose Tissue Inflammation and Dysregulated Adipokine Profimentioning

confidence: 99%

See 2 more Smart Citations

Adipokine dysregulation and adipose tissue inflammation in human obesity

Unamuno

Gómez-Ambrosi

Rodrı́guez

et al. 2018

Eur J Clin Investigation

Self Cite

478

331

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“…FGF21 is known to decrease during weight loss (33–35), and one group reported FGF21 reduction in response to rosiglitazone in patients with Type 2 diabetes (36), but these studies did not demonstrate associations with liver fat. To our knowledge, there are limited reports to date of changes in FGF21 in association with liver fat reduction.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

Braun

Feldpausch

Czerwonka

et al. 2017

Growth Hormone & IGF Research

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Objective Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans. Methods 50 HIV-infected men and women with increased abdominal adiposity participated in this randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo daily for six months. Fasting laboratory measures, liver fat by 1H-magnetic resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly selected subset. Results At baseline, serum log10 FGF21 was significantly associated with log10 liver fat (r=0.32, p=0.03). Log10 FGF21 tended to decrease in the tesamorelin group compared to placebo (p=0.06). Among the entire cohort, reductions in FGF21 were significantly associated with reductions in liver fat (ρ=0.41, p=0.01), log10 gamma glutamyl tran speptidase (GGT, r=0.40, p=0.009), and FIB4 index (r=0.37, p=0.02). Conclusions In HIV-infected individuals, FGF21 is significantly positively associated with liver fat. FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve. Moreover, these data suggest that tesamorelin improves liver fat via pathways other than increasing serum FGF21.

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Obese asthma phenotypes display distinct plasma biomarker profiles

Björkander

Klevebro

Hernandez‐Pacheco

et al. 2023

Clinical & Translational All

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Background Obese asthma is a complex phenotype and further characterization of the pathophysiology is needed. This study aimed to explore inflammation‐related plasma biomarkers in lean and overweight/obese asthmatics. Methods We elucidated levels of inflammation‐related plasma proteins in obese asthma phenotypes in the population‐based cohort BAMSE (Swedish: Children, Allergy, Milieu, Stockholm, Epidemiology) using data from 2069 24‐26‐year‐olds. Subjects were divided into lean asthma (n = 166), lean controls (n = 1440), overweight/obese asthma (n = 73) and overweight/obese controls (n = 390). Protein levels (n = 92) were analysed using the Olink Proseek Multiplex Inflammation panel. Results Of the 92 included proteins, 41 were associated with lean and/or overweight/obese asthma. The majority of proteins associated with overweight/obese asthma also associated with overweight/obesity among non‐asthmatics. Beta‐nerve growth factor (BetaNGF), interleukin 10 (IL‐10), and matrix metalloproteinase 10 (MMP10) were associated only with lean asthma while C‐C motif chemokine 20 (CCL20), fibroblast growth factor 19 (FGF19), interleukin 5 (IL‐5), leukemia inhibitory factor (LIF), tumor necrosis factor ligand superfamily member 9 (TNFRSF9), and urokinase‐type plasminogen activator (uPA) were associated only with overweight/obese asthma. Overweight/obesity modified the association between asthma and 3 of the proteins: fibroblast growth factor 21 (FGF21), interleukin 4 (IL‐4), and urokinase‐type plasminogen activator (uPA). In the overweight/obese group, interleukin‐6 (IL‐6) was associated with non‐allergic asthma but not allergic asthma. Conclusion These data indicate distinct plasma protein phenotypes in lean and overweight/obese asthmatics which, in turn, can impact upon therapeutic approaches.

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FGF19 and FGF21 serum concentrations in human obesity and type 2 diabetes behave differently after diet- or surgically-induced weight loss

Cited by 138 publications

References 41 publications

Adipokine dysregulation and adipose tissue inflammation in human obesity

Adipokine dysregulation and adipose tissue inflammation in human obesity

Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

Obese asthma phenotypes display distinct plasma biomarker profiles

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