Fibroblast growth factor 21 (FGF-21) in obese children: no relationship to growth, IGF-1, and IGFBP-3

AbstractBackground:Fibroblast growth factor 21 (FGF-21) is a hepatic protein that plays a critical role in liver, adipose tissue, and bone metabolism. Animal models reported an increase of FGF-21 and associated growth disturbances in undernutrition. Therefore, we studied the impact of weight loss in obese children on growth, FGF-21, and insulin-like factor 1 (IGF-1) concentrations.Methods:We analyzed height, serum concentrations of FGF-21, IGF-1, IGFBP-3, leptin, and insulin at baseline and 1 year later in 30 obese children with substantial weight loss (reduction >0.5 BMI-SDS) and in 30 obese children of similar age, gender, and pubertal stage with stable BMI-SDS. All children participated in a 1-year lifestyle intervention. Height and IGF-1 was transformed to standard deviation score (SDS). Multiple linear regression analyses adjusted for age, gender, and pubertal stage were performed.Results:At baseline, height-SDS was significantly related to IGF-1-SDS (β-coefficient 0.68 95% confidence interval (95% CI)±0.49; p=0.008) and leptin (β-coefficient 0.042 95% CI±0.030; p=0.008), but not to FGF-21 or insulin. FGF-21 was not significantly associated with IGF-1 or IGFBP-3. In longitudinal analysis, changes of FGF-21 were not significantly related to changes of height, IGF-1-SDS or IGFBP-3. However, in the subgroup of 30 children with substantial BMI-SDS reduction, FGF-21, leptin, insulin, and HOMA decreased significantly.Conclusion:As there was no significant association between FGF-21 and growth or IGF-1 both in cross-sectional and longitudinal analyses, these findings do not support the hypothesis that FGF-21 is involved in growth of obese children. Further studies are necessary to understand the multiple alterations in the growth hormone (GH) axis in obese children.

Download Full-text

Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

Gastroenterology Research and Practice ◽

10.1155/2017/3089378 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Liming Liu ◽

Cuiqing Zhao ◽

Ying Yang ◽

Xiaoxia Kong ◽

Tuo Shao ◽

...

Keyword(s):

Adipose Tissue ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Critical Role ◽

Experimental Colitis ◽

Fibroblast Growth Factor 21 ◽

Lipolytic Enzyme ◽

Fibroblast Growth ◽

Adipose Tissue Lipolysis ◽

The Impact

Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT) lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS) ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO) mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21) treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA) and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

Download Full-text

The impact of LDLR function on fibroblast growth factor 21 levels

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.05.032 ◽

2015 ◽

Vol 241 (2) ◽

pp. 322-325

Author(s):

Joost Besseling ◽

Kwok Leung Ong ◽

Roeland Huijgen ◽

Kerry-Anne Rye ◽

G.Kees Hovingh ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

The Impact

Download Full-text

Transient postprandial increase in intact circulating fibroblast growth factor-21 levels after Roux-en-Y gastric bypass: a randomized controlled clinical trial

PeerJ ◽

10.7717/peerj.11174 ◽

2021 ◽

Vol 9 ◽

pp. e11174

Author(s):

Mette S. Nielsen ◽

Susanna Søberg ◽

Julie B. Schmidt ◽

Anne Chenchar ◽

Anders Sjödin ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Growth Factor ◽

Energy Balance ◽

Fibroblast Growth Factor ◽

Negative Energy ◽

Negative Energy Balance ◽

Fibroblast Growth Factor 21 ◽

Control Group ◽

Fibroblast Growth

Background Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21. Method Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. The 28 participants were randomized to undergo RYGB surgery at week 8 (RYGB group, n = 14), or to a control group scheduled for surgery at week 12 (n = 14). Fasting levels of intact, biologically active FGF21 (amino acids 1-181) and its postprandial responses to a mixed meal were assessed at week 7 and 11, and 78 weeks (18 months) after RYGB. Results At week 11 (3 weeks after RYGB), postprandial responses of intact FGF21 were enhanced in participants undergoing surgery at week 8 (change from week 7 to 11: P = 0.02), whereas no change was found in non-operated control participants in similar negative energy balance (change from week 7 to 11: P = 0.81). However, no between-group difference was found (P = 0.27 for the group-week-time interaction). Fasting, as well as postprandial responses in intact FGF21, were unchanged 18 months after RYGB when both the RYGB and control group were collapsed together (change from week 7 to 78 weeks after RYGB: P = 0.17). Conclusion Postprandial intact FGF21 levels were enhanced acutely after RYGB whereas no signs of sustained changes were found 18 months after surgery. When comparing the acute effect of RYGB with controls in similar negative energy balance, we failed to detect any significant differences between groups, probably due to the small sample size and large inter-individual variations, especially in response to surgery.

Download Full-text

Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00265.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. G661-G672 ◽

Cited By ~ 2

Author(s):

Christian Zinck Jensen ◽

Kirstine N. Bojsen-Møller ◽

Maria S. Svane ◽

Line M. Holst ◽

Kjeld Hermansen ◽

...

Keyword(s):

Gastric Bypass ◽

Growth Factor ◽

Bile Acids ◽

Fibroblast Growth Factor ◽

Gut Hormones ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Control Subjects ◽

Hormone Responses ◽

The Impact

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), and we investigated the impact of glucose, protein, and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids, and fibroblast growth factor 21 (FGF-21) after RYGB and in nonoperated control subjects. In a randomized, crossover study 10 RYGB operated and 8 healthy weight-matched control subjects were administered 4 different 4-h isocaloric (200 kcal) liquid meal tests containing >90 energy (E)% of either glucose, protein (whey protein), or fat (butter with and without orlistat). The primary outcome was glucagon-like peptide-1 (GLP-1) secretion (area under the curve above baseline). Secondary outcomes included responses of peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glicentin, neurotensin, ghrelin, insulin, glucagon, bile acids, and FGF-21. In the RYGB group the responses of GLP-1, GIP, glicentin, FGF-21, and C-peptide were increased after glucose compared with the other meals. The neurotensin and bile acids responses were greater after fat, while the glucagon and CCK responses were greater after protein ingestion. Furthermore, compared with control subjects, RYGB subjects had greater responses of total PYY after glucose, glucagon after glucose and fat, glicentin after glucose and protein, and GLP-1 and neurotensin after all meals, while GIP and CCK responses were lower after fat. Ghrelin responses did not differ between meals or between groups. Orlistat reduced all hormone responses to fat ingestion, except for ghrelin in the RYGB group. In conclusion, after RYGB glucose is a more potent stimulator of most gut hormones, especially for the marked increased secretion of GLP-1 compared with fat and protein. NEW & NOTEWORTHY We investigated the impact of glucose, protein, and fat meals on intestinal and pancreatic hormones, bile acid, and fibroblast growth factor 21 (FGF-21) secretion in gastric bypass-operated patients compared with matched nonoperated individuals. The fat meal was administered with and without a pancreas lipase inhibitor. We found that the impact of the different meals on gut hormones, bile, and FGF 21 secretion differ and was different from the responses observed in nonoperated control subjects.

Download Full-text

Changes in Fibroblast Growth Factor 21 with Modest Weight Loss

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000401854.63730.9f ◽

2011 ◽

Vol 43 (Suppl 1) ◽

pp. 669

Author(s):

Laurel A. Littlefield ◽

Robert L. Bowers ◽

Felipe Araya-Ramirez ◽

A Jack Mahurin ◽

J Kyle Taylor ◽

...

Keyword(s):

Weight Loss ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Modest Weight Loss

Download Full-text

Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges

International Journal of Molecular Sciences ◽

10.3390/ijms20194692 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4692 ◽

Cited By ~ 5

Author(s):

Úrsula Martínez-Garza ◽

Daniel Torres-Oteros ◽

Alex Yarritu-Gallego ◽

Pedro F. Marrero ◽

Diego Haro ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Metabolic Response ◽

Therapeutic Potential ◽

Metabolic Effects ◽

Fibroblast Growth Factor 21 ◽

Signal Pathways ◽

Fibroblast Growth ◽

The Impact

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis. This review is focused on describing individually the FGF21-dependent metabolic response activated by some of the most common nutritional challenges, the signal pathways triggering this response, and the impact of this response on global homeostasis. We consider that this is essential knowledge to identify the potential role of FGF21 in the onset and progression of some of the most prevalent metabolic pathologies and to understand the potential of FGF21 as a target for these diseases. After this review, we conclude that more research is needed to understand the mechanisms underlying the role of FGF21 in macronutrient preference and food intake behavior, but also in β-klotho regulation and the activity of the fibroblast activation protein (FAP) to uncover its therapeutic potential as a way to increase the FGF21 signaling.

Download Full-text