Reduced acylated ghrelin concentrations have been found in research at high altitude (e.g. http://www.ncbi.nlm.nih.gov/pubmed/22114179). Can anyone think of a mechanism behind the reduction? I believe total ghrelin levels remain unaltered at altitude, thus suggesting that it is the acylation that is being effected by low oxygen levels rather than the secretion of ghrelin. The acylation is an estrification reaction between ghrelin and a medium chain fatty acid, catalysed by ghrelin-O-acyl transferase. This posttranslational modification is necessary for ghrelin to bind to GHS-R to exert its biological actions. From my reading estrification is not directly reliant on molecular oxygen. Some have suggested that the acylation occurs in the liver and at altitude there may be a reduced blood flow to the liver. However, more recent work suggests that the acylation occurs in the stomach and on top of this other work suggests that there is not a reduced blood flow to the liver at altitude.
Can anyone think of a mechanism behind the reduced acylated ghrelin concentrations at high altitude (low oxygen environment)?
Thanks,
Jamie
The paper below suggests that increased aerobic exercise can lead to reduced acylated ghrelin levels. Perhaps the high altitude is working as aerobic exercise which, theortetically, would also reduce the acylated ghrelin levels in the blood.
Other than that, I believe that your biochemistry is spot on and probably is not related to reduced blood flow to the liver.
A study published in the International Journal of Obesity found a strong association --no correlation proved of course-between altitude and obesity prevalence within the United States. Using data for over 400,000 people, researchers found Americans living closest to sea level were four to five times more likely to be obese, compared to people who live well above sea level in Colorado.
#2 This, info directly below, provides an excellent review of GOAT, enzyme involved in ghrelin acetylation.
Stengel A, Wang L, Taché Y. Stress-related alterations of acyl and desacyl ghrelin circulating levels: mechanisms and functional implications. Peptides. 2011;32(11):2208-2217. doi:10.1016/j.peptides.2011.07.002.
#3 This article in Appetite June 2015 follows your line of thought http://www.sciencedirect.com/science/article/pii/S0195666315000665
http://www.sciencedirect.com/science/article/pii/S0195666315000665
#4 I have found this info in general hard to sort. You note: "I believe total ghrelin levels remain unaltered at altitude" but a few studies go against this so I am not holding my breath... LOL
The studies arguing a rise in ghrelin are older but --makes one wonder about what is really going on. Why is there this variation?
One of the studies is online at: http://www.eje-online.org/content/166/6/969.full.pdf
Ghrelin Rises
Conclusions: After 14 days of exposure to HA, we observed a significant ghrelin and GH increase without changes in GHBP, IGF1, IGF2, IGFBP3, ALS, and insulin. Higher GH seems to be needed for acute metabolic effects rather than IGF/IGFBP3 generation. Increased IGFBP1 and -2 may reflect effects from HA on IGF bioavailability.
European Journal of Endocrinology 166 969–976
# 5 This article is not completely translated and is on rats. High altitude made Ghrelin rise. Poor rats
Introduction: A high-altitude environment causes appetite loss in unacclimatised humans, leading to weight reduction. Ghrelin, cholecystokinin
(CCK), and glucagon like peptide-1 (GLP-1), are gut hormones involved in the regulation of food intake and energy metabolism. The liver is an important site of metabolic regulation, and together with the gut it plays a role in food intake regulation. This study intends to study the time dependent changes occurring in plasma gut hormones, PPARα, PPARδ, and PGC1α, in the stomach and liver during hypoxia.
Material and methods: Male Sprague Dawley rats were exposed to hypobaric hypoxia in a decompression chamber at 7620 m for different durations up to seven days.
Results: Hypoxia increased circulating ghrelin from the third day onwards while CCK and GLP-1 decreased immediately. An increase in ghrelin, ghrelin receptor protein levels, and GOAT mRNA levels in the stomach was observed. Stomach cholecystokinin receptor (CCKAR), PPARα, and PPARδ decreased. Liver CCKAR decreased during the first day of hypoxia and returned to normal levels from the third day onwards. PPARα and PGC1α expression increased while PPARδ protein levels reduced in the liver on third day.Conclusion: Hypoxia alters the expression of ghrelin and ghrelin receptor in the stomach, CCKAR in the liver, and PPAR and its cofactors,
which might be possible role players in the contribution of gut and liver to anorexia at high altitude. (Endokrynol Pol 2015; 66 (4): 334–341)
#6 In support of your point : (and may be whom you were reviewing?)
Influence of rest and exercise at a simulated altitude of 4,000 m on appetite, energy intake, and plasma concentrations of acylated ghrelin and peptide YY.
Wasse LK1, Sunderland C, King JA, Batterham RL, Stensel DJ.
#7 Drop in total Ghrelin at altitude
Nutr Neurosci. 2005 Jun;8(3):161-5.
Ghrelin and leptin levels of sojourners and acclimatized lowlanders at high altitude.
Shukla V1, Singh SN, Vats P, Singh VK, Singh SB, Banerjee PK.
#8 Rise in total Ghrelin at altitude
Eur J Endocrinol June 1, 2012 166 969-976
Adaptation of ghrelin and the GH/IGF axis to high altitude
Stefan Riedl, Michael Kluge1, Katharina Schweitzer2, Thomas Waldhör3 and Herwig Frisch
Sorry much is not on target to your central query. Always been puzzled by the varied results of total ghrelin at altitude.
Best, Marybeth Lambe MD FAAFP