Differences

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--- gdf15 [2026/08/11 00:01] – [Actions] gary1
+++ gdf15 [2026/08/11 00:05] (current) – gary1
@@ Line 16: / Line 16: @@
   *the human GDF15 gene is located on the forward strand of the short arm of chromosome 19 (19p13.11), flanked by the pyroglutamyl-peptidase I (PGPEP1) and leucine rich repeat containing 25 (LRRC25) genes upstream and downstream, respectively (([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299427/]]))
   *expression of its gene is one of the genes enriched in a model system of macrophage activation
-  *it acts via the GFRAL receptor
+  *it acts via the GFRAL receptor which is predominately expressed in the hindbrain
 =====Actions=====
   *acts on the brain stem centres via GFRAL receptors where it causes anorexia and nausea, and regulates appetite and body weight
+    * activates the hypothalamic-pituitary-adrenal (HPA) axis, stimulating ACTH release which then stimulates adrenal cortisol production
+    * increases sympathetic nervous system (SNS) activity to the liver, adipose tissue, and muscle
   *potential important regulatory actions on embryogenesis in keeping with its placental origin
   *inhibits the secretion of tumor necrosis factor-α (TNF-α) from macrophages in response to lipopolysaccharide (LPS)
-  *in patients with [[steatohepatitis|metabolic dysfunction-associated steatohepatitis]] it can suppress liver inflammation and slow the progression of liver scarring independently of weight loss
+  *in patients with [[steatohepatitis|metabolic dysfunction-associated steatohepatitis]] levels are high and it can suppress liver inflammation and slow the progression of liver scarring independently of weight loss
     * GDF15 activates signalling from the brain to the nervous system independent of β-adrenergic signaling that leads to the release of glucocorticoids which help dampen inflammation in the liver and those protective effects occur independently of changes in food intake, body weight or liver fat (([[https://www.sciencedirect.com/science/article/pii/S1550413126002810?via%3Dihub|2026: GDF15 suppresses liver inflammation independently of weight loss through neuroendocrine glucocorticoid signaling]]))
 =====Normal physiologic state=====
   *"Under normal non-pregnant physiological conditions, circulating GDF15 levels are low, typically less than 1000 pg/ml, but are increased by a wide range of acute stressors such as sepsis and inflammation, and are characteristically persistently elevated in a number of chronic disease states, for example reaching levels of 10,000–100,000 pg/ml in patients with advanced cancers" " It is markedly elevated at birth at concentrations of 3000 pg/ml, declining to levels within the healthy adult normal range within the first 4 months of life"  (([[https://www.sciencedirect.com/science/article/abs/pii/S245196502100096X]]))
@@ Line 35: / Line 38: @@
   *increasing age: GDF15 levels changed by 11% on average after 5 years of follow-up, and is a biomarker of age
-=====Other causes of increased serum levels result=====
+=====Other causes of increased serum levels=====
   *pregnancy - produced by the feto-placental unit in large amounts and in those with prenatally low levels of GDF15 and thus sensitive to higher levels, are at higher risk of developing **[[hyperemesis_gravidarum]]** (([[https://www.nature.com/articles/s41586-023-06921-9|Nature 2023. GDF15 linked to maternal risk of nausea and vomiting during pregnancy]]))
   *patients with beta thallaesaemia