glyphosate and lipids

Enterohepatic circulation of glyphosate? [1]

Glyphosate and thiols examined the reaction of protein thiols with glyphosate. Enzymes involved in lipid metabolism seemed to be particularly targeted.

A previous post on this site examined use of Klinobind to stop the enterohepatic circulation of toxins related to smoking. There really does not seem to be strong evidence for glyphosphate enterohepatic circulation. The closest I could find was a Chinese publication that examined the enterohepatic circulation effects of glyphosate in grass carp. [1] These authors detected glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA) in the gut.

They also noted GI inflammation, barrier damage, and hepatic steatosis in carp exposed to glyphosate. Changes in the lipid profile were noted in visceral fat and the serum. Glyphosate decreased recirculating and secondary bile acids. [1] Cyp27a1, cyp8b1 and fxr were also down regulated. The abstract only noted an increase in lipopolyscacharide. The dysregulation of the gut-liver axis possibly resulted in ultimate lipid metabolism disorder according to these authors. [1]

• cyp27a1 is a cytochrome P450 responsible for cholesterol homeostasis and bile acid production. Cholesterol 7 alpha-hydroxylase has its own Wikipedia page that is a little better than the AI Uniprot page. Wikipedia authors mention negative feedback regulation by Fxr.
• ALT and AST are liver enzymes that appear in the blood when the liver is injured. Triglycerides go down.
• Cyp8b1 is A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis.
  Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH–hemoprotein reductase) (By similarity
• Fxr, Farnesoid X receptor, is a family of transcription factors that bind chenodeoxycholic acid and other bile acids. The complex translocates to the cell nucleus and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes. Activated FXR suppresses cholesterol 7 alpha-hydroxylase (CYP7A1),
• ALT, AST, and AKP are liver enzymes that are only in the blood when the liver is injured.
• In a survey of human microsomes, glyphosate, CYP2C9, IC(50) = 3.7 micro M PubMed. Free paper Sci-Hub

Glyphosate disrupts lipid metabolism in humans[2]

This study came from the Jiangsu Province in China. A total of 391 participants were recruited from Jiangsu province, China, 307 of which were glyphosphate based herbicide GBHs production workers from three different chemical factories who were compared to 84 were healthy participants from the same region who had never been exposed to glyphosate.

a select cholesterol ester rules the list of serum lipids that change

The following is a highly edited Table 1. There were so many increased lipids in the glyphosate factory workers I am only presenting the lipids that increased 100x (Fold Change) or more. Just for presentation I kept one marker that actually decreased in the glyphosate factory workers.

lipid changes in glyphosate workers compared to office workers

The Zhang publication had one figure in particular that I thought gave a bird’s eye view of what was going on. This is a rather lop sided volcano plot of lipid changes. Most of the serum lipids are increasing in the exposed group compared to the office worker controls. Just a few phosphatidyl choline lipids are going down compared to the controls.

Volcano plots can be difficult to read. The X-axis is the fold change in log base 2 instead of log₁₀ that most of us are more familiar with.

X-axis

-2, 0, 2, 4, 6 0.5x, 1x, 4x, 16x, 64x

Y-axis

We are back to log₁₀ of the probability of these changes not being due to random

0, 1.3, 50, 100, 150 ….. 1 the same, 0.05 or 95% certain not due to random chance. All points above the dotted line in the graph are changes that we are >95% are not due to random chance.

fatty acid abbreviations

• fatty acid (FA)
• diacylglycerols (DG)
• cholesteryl esters (CE)
• ceramides (Cer)
• sphingomyelins (SM)
• lysophosphatidylethanolamines (LPE)
• phosphatidylcholines (PC)
• lysophosphatidylcholines (LPC)
• triacylglycerols (TG), fatty acids (FA)
• phosphatidylethanolamines (PE)

some examples of fats

Phosphatidyl choline is a standard lipid bilayer phospholipid. We have a head group called choline on carbon of the three carbon molecule glycerol. An example from PubChem is shown with palmitic acid and oleic acid as the fatty acids on carbons 2 and 3. Palmitic acid has only 16 carbons. Oleic acid has 18 carbons and one double bond. We have something similar to this species increasing in the workers exposed to glyphosate. Strangely we see a huge decrease in a phosphatidyl choline decreasing with just one fatty acid with 46 carbons in the glycophosphate exposed workers.

Are North Americans exposed to glyphosate in their food?

The Food Navigator has some interesting things to say about glyphosate used as a weed killer while select crops are being dried prior to harvest. A Canadian study used mass spectrometry to detect glyphosate and it’s metabolite AMPA in banked urine samples from pregnant women. [3] Both chemicals were detected in the urine of most of the expectant mothers. Analyses of multiple factors led the investigators to speculate that the diet of this predominantly urban cohort was the source of exposure. [3] A U.S. followup studies used urine samples of post menopausal women in California. In this study scrupulous notes were taken of the recalled diets of these women. [4] Grains were concluded to be the source of glyphosate exposure whereas soy and wine were the source of the metabolite AMPA. [4]

The EWG has actually published some glyphosate numbers of oat based productions over the past few years as well as legumes. This NIST.gov site has an interesting quote. “Oats are unique, as grains go,” said NIST researcher Jacolin Murray. “We chose oats as our first material because food producers use the glyphosate as a desiccant to dry out the crop before they harvest it. Oats tend to have a high amount of glyphosate.” Crop desiccation allows for an earlier harvest and improves uniformity of crops. Because of its wide use, glyphosate is typically found at higher levels compared with other pesticides, according to co-author Justine Cruz.

References

1. Yan B, Sun Y, Fu K, Zhang Y, Lei L, Men J, Guo Y, Wu S, Han J, Zhou B. Effects of glyphosate exposure on gut-liver axis: Metabolomic and echanistic analysis in grass carp (Ctenopharyngodon idellus). Sci Total Environ. 2023 Aug 4;902:166062. PubMed
2. Zhang F, Zhang Q, Liu X, Gao M, Li X, Wang Y, Chang Y, Zhang X, Huo Z, Zhang L, Shan J, Zhu B, Yao W. Human serum lipidomics analysis revealed glyphosate may lead to lipid metabolism disorders and health risks. Environ Int. 2023 Jan;171:107682. free paper
3. Ashley-Martin J, Huang R, MacPherson S, Brion O, Owen J, Gaudreau E, Bienvenu JF, Fisher M, Borghese MM, Bouchard MF, Lanphear B, Foster WG, Arbuckle TE. Urinary concentrations and determinants of glyphosate and glufosinate in pregnant Canadian participants in the MIREC study. Environ Res. 2023 Jan 15;217:114842. free article
4. McGilvrey M, Hegde AM, Pirrotte P, Park HL. Urinary glyphosate and AMPA levels in a cross-sectional study of postmenopausal women: Associations with organic eating behavior and dietary intake. Int J Hyg Environ Health. 2023 Jul;252:114211. PMC free article