Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity

Schernthaner-Reiter, Marie Helene; Kasses, Dominik; Tugendsam, Christina; Riedl, Michaela; Peric, Slobodan; Prager, Gerhard; Krebs, Michael; Promintzer-Schifferl, Miriam; Clodi, Martin; Luger, Anton; Vila, Greisa

doi:10.1530/eje-16-0550

Cited by 43 publications

(24 citation statements)

References 25 publications

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“…As GDF15 administration causes weight loss and mice lacking GDF15 are prone to gain weight on an HFD, we determined whether GDF15 shares any features in common with known hormonal regulators of post-prandial satiety (e.g., enteroendocrine hormones such as GLP-1) or longer term hormonal regulators of nutrient stores (e.g., leptin). In contrast to GLP-1, and consistent with previous reports ( Schernthaner-Reiter et al., 2016 , Tsai et al., 2015 ), GDF15 did not respond acutely to a meal or a glucose load in humans. In mice fasted for 24 h, there was no change in circulating GDF15, whereas the predicted fall in leptin levels and rise in FGF21 levels was seen.…”

Section: Discussionsupporting

confidence: 91%

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

et al. 2019

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Summary GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Circulating GDF15 levels manifest very modest changes in response to moderate caloric surpluses or deficits in mice or humans, differentiating it from classical intestinally derived satiety hormones and leptin. However, GDF15 levels do increase following sustained high-fat feeding or dietary amino acid imbalance in mice. We demonstrate that GDF15 expression is regulated by the integrated stress response and is induced in selected tissues in mice in these settings. Finally, we show that pharmacological GDF15 administration to mice can trigger conditioned taste aversion, suggesting that GDF15 may induce an aversive response to nutritional stress.

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Section: Discussionsupporting

confidence: 91%

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

et al. 2019

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“…In fact, both metformin and hyperglycaemia are known to interfere with mitochondrial bioenergetics. Moreover, high glucose in human umbilical endothelial cells and in HepG2 cells is able to promote GDF‐15 expression and secretion, and, in participants without diabetes, glucose ingestion is associated with an elevation of plasma GDF‐15 levels …”

Section: Discussionsupporting

confidence: 74%

“…HepG2 cells 12 is able to promote GDF-15 expression and secretion, and, in participants without diabetes, glucose ingestion is associated with an elevation of plasma GDF-15 levels. 13 The results of the present study confirm that current smoking is associated with elevated GDF-15, 14 but the association with smoking exposure was stronger than with current smoking status; therefore, we suggest that it is chronic damage to pulmonary structures 15 that results in a persistent GDF-15 upregulation. Similarly, as circulating GDF-15 levels are strongly correlated with its intra-renal expression, 16 we interpret the association with plasma creatinine as a reflection of chronic kidney damage.…”

Section: And Insupporting

confidence: 73%

Metformin is the key factor in elevated plasma growth differentiation factor‐15 levels in type 2 diabetes: A nested, case–control study

Natali

Nesti

Venturi

et al. 2018

Diabetes Obesity Metabolism

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Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case-control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.

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“…One study had consistent findings that GDF15 decreased first and increased back to baseline levels at 120 min in OGTT. 26 Although Patal 17 et al suggested that GDF15 levels were unchanged following glucose ingestion, their data showed circulating GDF15 levels briefly fell at 60 min time point after the mixed meal. This variation trend was also similar to our results.…”

Section: Discussionmentioning

confidence: 94%

Increased Serum GDF15 Related to Improvement in Metabolism by Lifestyle Intervention Among Young Overweight and Obese Adults

Cai

Wang

et al. 2021

DMSO

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Growth differentiation factor 15 (GDF15) is closely related to obesity. This study aimed to explore the influence of weight loss intervention on serum GDF15 levels and the relationship between GDF15 and metabolism. Materials and Methods: Forty-four overweight and obese adults either adopted a lowcarbohydrate diet or performed moderate-to-vigorous exercise for 3 weeks. Weekly follow-ups were conducted to measure body composition, glucose and lipid metabolism and serum GDF15 levels. Results: After 3 weeks of intervention, body weight, fat mass and waist circumference in both groups decreased (P < 0.05). No significant change in GDF15 levels was observed in the two groups. Among all the subjects, 10 of them (22.7%, group of Down) showed a decrease in GDF15 and 34 (77.3%, group of Up) showed an increase in GDF15 after the intervention. We found that GDF15 increased significantly with the follow-up time in the UP group and waist circumference, fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglycerides (TG) decreased (P for trend <0.05). However, no significant differences in all parameters were detected in Down group. In addition, GDF15 was elevated between 30 mins and 120 mins in a 75-g oral glucose tolerance test. Its trend was negatively correlated with plasma glucose and serum insulin. Conclusion: Increased serum GDF15 was associated with improvement in metabolism by lifestyle intervention among young overweight and obese adults. The increase of GDF15 could be an indicator to evaluate metabolic improvements in overweight and obese people. Clinical Trial Registration: www.chictr.org.cn, registration number ChiCTR1800016786.

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Growth differentiation factor 15 increases following oral glucose ingestion: effect of meal composition and obesity

Abstract: In summary, high glucose and insulin peaks upregulate GDF15 transcription and release. The nutrient-induced increase in GDF15 levels depends on rapid glucose and insulin excursions following fast-digesting carbohydrates, but not on the amount of calories taken in.

Cited by 43 publications

References 25 publications

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans

Metformin is the key factor in elevated plasma growth differentiation factor‐15 levels in type 2 diabetes: A nested, case–control study

Increased Serum GDF15 Related to Improvement in Metabolism by Lifestyle Intervention Among Young Overweight and Obese Adults

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