Song, M., Li, X., Zhang, X., Shi, H., Vos, M. B., Wei, X., Wang, Y., Gao, H., Rouchka, E. C., Yin, X., Zhou, Z., Prough, R. A., Cave, M. C., & McClain, C. J. (2018). Dietary copper-fructose interactions alter gut microbial activity in male rats. American journal of physiology. Gastrointestinal and liver physiology, 314(1), G119–G130. PMC free article
These authors started with the knowledge that too little and perhaps too much copper can lead to non-alcoholic fatty liver diseae (NAFLD). Fructose was also considered a contributor to NAFLD. what we at CopperOne think is really cool is that these investigators also lookd at the intestinal bacteria.
Male weanling Sprague-Dawley rats (35–45 g) were fed a purified AIN-76 diet with Cu(II)CO3. A purified AIN-76-based diet containing nearly 40% sucrose (wt/wt).
- 1.6, marginal Cu
- 6.0 adequate Cu
- 20 ppm supplemental Cu
- The mice were given distilled water to drink ± 30% weight/volume fructose.of copper as marginal, adequate, or supplemental doses, respectively, for 4 wk. Control animals
How much sugar, presumably fructose, is in Coca Cola? This site says that there are 25 g sugar in 7.5 oz. Using the online conversion, this is 213 mL. This comes out to 12% w/v! These little animals were drinking water that had almost 3x as much sugar as Coca Cola. Does this measure the human condition? Humans who are consuming high fructose corn syrup sweetened beverages are probably also consuming foods sweetened with the same.
Copper and copper proteins
- Ceruloplasmin…The Cu carrier protein in the plasma saw a big reduction in the Cu marginal rats. Drinking fructose resulted in a ~25% reduction in the Cu adequate rats.
- Plasma Cu, The plasma is the portion of blood not containing cells and clotting factors. Fructose in the drinking water increased the serum Cu in the Cu supplemented group.
- Liver Cu, Both marginal and supplemented Cu diets showed liver Cu than the fructose free Cu adequate rats.
- Duodenal Ctr1 Fructose in the drinking water decreased mRNA levels that code for the protein Ctr1 in Cu marginal and Cu supplemented rats. Fructose has no effect on Ctr1 mRNA in Cu adequate rats
- Liver Ctr1. All treatments decreased liver Ctr1 mRNA compared to the Cu adequate rats that were not drinking fructose.
Two liver enzymes and a cytokine
When liver enzymes end up in the blood, it is a sign of liver damage. These authors looked at ALT and AST. These enzymes did not track each other from one diet to the next. The high fructose/Cu supplement diet seemed to be most consistently associated with liver damge. MCP-1, macrophage chemoattractant protein 1, recruits immune cells to he site of an infection. Cu marginal and supplemented diets tended to increase MCP-1 in their Cu adequate counterparts.
Bacteria and leaky guts
Endotoxin/lipopolysaccharide is a lipid component of the cell membranes of Gram negative bacteria. Marginal Cu increased the amount of LPS in the blood. LPS binding protein LBP is produced in the intestine, liver, and adipose tissue. In each of the three diet groups, fructose increased LBP relative to unadulterated drinking water. FD-4, 100uL of FITC-dextran (molecular weight 4,000, FD-4, 40 mg/ml) were injected into the lumen before the gut was ligated to form a sac. The gut sac was then placed in Krebs-Henseleit bicarbonate buffer and incubated at 37°C for 20 min. The FD-4 that penetrated from the lumen into the incubation buffer was measured spectrofluorometrically with an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Only the combination of Cu supplementation and fructose adulterated drinking water caused leaky gut.
Of mucin secreting goblet cells, tight junctions….
Goblet cells are mucin secreting cells of the GI tract. The PAS stain, periodic acid is reacting with mucin
In copper adequate and copper supplemented, the presence of fructose in the drinking water seems to decrease the length of the villi.
Counting bugs
Song and coworkers got quite sophisticated in their counting that we will not get into. Instead we will only present a bar graph in figure 4.
The one thing that stands out is the down sizing of Verrucomicrobia, that Wikipedia authors have little to say about. Given the high sugar content of these rat’s diets, any difference needs to be taken with a certain level of skepticism.
We’d like to make note of a second time, Cu used in this study was Cu(II)CO3. We at CopperOne would tend to think that the results would have been different with Cu in the +1 oxidation state.
This is just a reminder that the interior mesenteric vein drains blood from the descending colon. If Cu(II) has deleterious effects on our gut bacteria, it will be felt in our livers. Changing the makeup of intestinal bacteria will change short chain fatty acids, polyamines, metabolites will affect our livers. If Cu(II) makes our guts more permeable, the LPS will be seen by the liver. It would be interesting to repeat this study with a diet that is a bit lower in sucrose.
Cuprous niacin 