FGF-21 Conducts a Liver-Brain-Kidney Axis to Promote Renal Cell Carcinoma

Li, Zongyu; Zhang, Xinyi; Zhu, Wanling; Zhang, Cuiling; Sadak, Katherine; Halberstam, Alexandra A.; Brown, Jason; Perry, Curtis J.; Bunn, Azia; Braun, David A.; Adeniran, Adebowale; Lee, Sang‐Won; Wang, Andrew; Perry, Rachel J.

doi:10.1101/2023.04.12.536558

Cited by 4 publications

(2 citation statements)

References 63 publications

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“…These data demonstrate that GDF15's primary hypoglycemia counterregulatory mechanism is to stimulate gluconeogenesis. To determine the source(s) of these changes in gluconeogenesis, we employed Renal Gluconeogenesis Analytical Leads (REGAL) 23,24 to distinguish the contributions of liver and kidney to whole-body glucose production. GDF15 upregulated, and anti-GDF15 inhibited, gluconeogenesis from both liver and kidney (Fig.…”

Section: Gdf15 Defends Against Hypoglycemia By Increasing Gluconeogen...mentioning

confidence: 99%

GDF15 is a Critical Renostat in the Defense Against Hypoglycemia

Zhang

Zhu

et al. 2023

Preprint

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Episodic hypoglycemia is one of the best honed, evolutionary conserved phenomena in biology, because of the constant feast-fast cycles that have characterized most of history. The counterregulatory response to hypoglycemia, mobilizing substrate stores to produce glucose, is the primary adaptive mechanism to enable survival. Catecholamines and glucagon have long been considered the key hypoglycemia counterregulatory hormones, but here we identify a new hypoglycemia counterregulatory factor. We employed the insulin tolerance test (ITT) and hyperinsulinemic-hypoglycemic clamp to mimic the two common settings in which hypoglycemia can occur in patients: postprandial insulin overdose and elevated basal insulin administration, respectively. We found that Growth Differentiation Factor 15 (GDF15) production is induced in the S3 segment of the renal proximal tubules and its release increases hepatic gluconeogenesis by increasing intrahepatic lipolysis in a beta-adrenergic receptor-2 (Adrb2)-dependent manner. In addition, mice exposed to recurrent hypoglycemia and patients with T1D exhibit impaired GDF15 production in the setting of hypoglycemia. These data demonstrate that GDF15 acts acutely as a gluco-counterregulatory hormone and identify a critical role for kidney-derived GDF15 in glucose homeostasis under physiological and pathophysiological conditions.

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Section: Gdf15 Defends Against Hypoglycemia By Increasing Gluconeogen...mentioning

confidence: 99%

GDF15 is a Critical Renostat in the Defense Against Hypoglycemia

Zhang

Zhu

et al. 2023

Preprint

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“…FGF-21 is a molecule that interconnects the liver-brain-kidney axis and promotes renal gluconeogenesis. Intriguingly, this process may contribute to the acceleration of the renal cell carcinoma progression ( Li et al, 2023 ).…”

Section: Eec Biology and Communication With The Kidneysmentioning

confidence: 99%

Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication

Nery Neto,

Yariwake,

Câmara

et al. 2023

Front. Pharmacol.

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Recent studies suggest that disruptions in intestinal homeostasis, such as changes in gut microbiota composition, infection, and inflammatory-related gut diseases, can be associated with kidney diseases. For instance, genomic investigations highlight how susceptibility genes linked to IgA nephropathy are also correlated with the risk of inflammatory bowel disease. Conversely, investigations demonstrate that the use of short-chain fatty acids, produced through fermentation by intestinal bacteria, protects kidney function in models of acute and chronic kidney diseases. Thus, the dialogue between the gut and kidney seems to be crucial in maintaining their proper function, although the factors governing this crosstalk are still emerging as the field evolves. In recent years, a series of studies have highlighted the significance of enteroendocrine cells (EECs) which are part of the secretory lineage of the gut epithelial cells, as important components in gut-kidney crosstalk. EECs are distributed throughout the epithelial layer and release more than 20 hormones in response to microenvironment stimuli. Interestingly, some of these hormones and/or their pathways such as Glucagon-Like Peptide 1 (GLP-1), GLP-2, gastrin, and somatostatin have been shown to exert renoprotective effects. Therefore, the present review explores the role of EECs and their hormones as regulators of gut-kidney crosstalk and their potential impact on kidney diseases. This comprehensive exploration underscores the substantial contribution of EEC hormones in mediating gut-kidney communication and their promising potential for the treatment of kidney diseases.

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Deregulating Cellular Metabolism

Mravec

2024

Neurobiology of Cancer

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FGF-21 Conducts a Liver-Brain-Kidney Axis to Promote Renal Cell Carcinoma

Cited by 4 publications

References 63 publications

GDF15 is a Critical Renostat in the Defense Against Hypoglycemia

GDF15 is a Critical Renostat in the Defense Against Hypoglycemia

Enteroendocrine cells and gut hormones as potential targets in the crossroad of the gut-kidney axis communication

Deregulating Cellular Metabolism

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