Lack of liver steatosis in germ-free mice following hypercaloric diets, serotonin causative

[Mauritio]

This is such an interesting study, once again underlining something RP has said for decades.

Rats that have a bacteria-free gut (germ free) dont experience the same weight gain that they normally experience on a "western" a.k.a. high PUFA diet. Not only that, but feeding them high fructose, which normally leads to fatty liver or even liver steatosis is absent in mice with a germ free gut.

"GF housing results in an impaired weight gain and a lack of steatosis following a WSD. Also the fructose-induced steatosis, which is unrelated to body weight changes, is absent in GF mice."

- Lack of liver steatosis in germ-free mice following hypercaloric diets - PubMed

This is interesting because it proves fructose does not cause fatty liver!
So it looks like fructose is feeding the wrong microbes, which then leads to an increase in serotonin and finally liver illnesses.


There is another recent study which shows exactly that: increasing serotonin (by lowering the serotonin transporter SERT), leads to a decrease in metabolism, weight gain and liver steatosis. The mice consumed 21% less calories, but still weighed more, which is saying something about serotonin's anti-metabolic effects.

"SERT-/- mice showed increased weight gain compared with SERT+/+ mice when fed a WSD ± F for 12 weeks (p < 0.05), whereby SERT-/- mice exhibited reduced energy (-21%) intake. Furthermore, SERT knockout resulted in a more pronounced liver steatosis (p < 0.05), enhanced levels of endotoxin in portal vein plasma (p < 0.05), and increased liver expression of Tnf and Myd88 (p < 0.05), when mice were fed a WSD ± F. "

"Our data demonstrate that SERT knockout causes weight gain, liver steatosis, and leaky gut, especially in mice fed a WSD. Therefore, SERT induction could be a novel therapeutic approach to improve metabolic diseases associated with intestinal barrier dysfunction."

- Serotonin reuptake transporter deficiency promotes liver steatosis and impairs intestinal barrier function in obese mice fed a Western-style diet - PubMed

 

[Mauritio]

Here is another study also showing increasing serotonin (by lowering SERT) leads to inflammation and fatty liver and that using a 5hT3 -antagonist attentuates the fatty liver, once again implicating serotonin in this disease.

"In fructose-fed mice treated with a 5-HT3 receptor antagonist, hepatic steatosis was significantly attenuated."

- Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice - PubMed

 

[Mauritio]

This study narrows it down further: fructose feeds the wrong microbes, that causes an increase in endotoxin ,which then activates TLR4 ,which then causes fatty liver. So once again: its not the fructose, but the gut ! This ties in well with another study I posted showing that fructose does not even reach the liver it is mostly metabolized by the intestines, so it makes sense that it will have its biggest imapact there.

"...the onset of fructose-induced NAFLD is associated with intestinal bacterial overgrowth and increased intestinal permeability, subsequently leading to an endotoxin-dependent activation of hepatic Kupffer cells."

- Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice - PubMed

 

[Candeias]

good finds! everything Ray had stated, ty