Varani et al., 2022 (NASH – Liver)
LIVER PROTEIN EXPRESSION IN NASH MICE ON A HIGH-FAT DIET
J Varani, SD McClintock, RN Knibbs, I Harber, D Zeidan, MAH Jawad-Makki & MN Aslam
Frontiers in Nutrition, 2022
Background:
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease globally. It is thought that 25% of adults accumulate fat in the liver (fatty liver) due to a high-fat Western diet (HFWD). This can progress to significant inflammation, cirrhosis and tumour formation. When these fatty deposits are followed by liver inflammation and damage the disease is called non-alcoholic steatohepatitis (NASH).
Methods:
Male NASH/FATZO mice were maintained on HFWD for 16 weeks +/- Aquamin Soluble (added to drinking water). Obeticholic acid (OCA) was used as positive control. OCA is in clinical trials as the only potential treatment for NASH. Mice maintained on standard (low-fat) chow were used as negative control. Body weight, liver weight, liver enzyme levels and liver histology were assessed, and samples obtained for protein profiling.
Results:
All HFWD mice had increased body weight, enlarged livers, increased liver enzymes, steatosis & hepatocyte degeneration (compared to the low-fat diet). There were multiple protein changes associated with dysregulated fat and carbohydrate metabolism, lipotoxicity and oxidative stress. Aquamin reduced liver toxicity and inflammation. The protein changes observed with mineral supplementation were not seen with OCA. Aquamin was shown to dramatically reduce the damaging downstream effects although steatosis itself was largely unaffected (Figure below left).
These results agree with our previous study (Aslam et al., 2012) where mice on HFWD for 18 months showed extensive liver inflammation and damage, steatosis, & tumour development.
Conclusions:
This current study identifies early (16-week) protein changes occurring in the livers of HFWD mice, and how Aquamin influences expression of these proteins. This work suggests Aquamin can prevent suppress NAFLD disease progression and further liver damage. Currently, there is no cure for NASH – OCA is in clinical trials as a potential treatment. Aquamin performs as well or better than OCA currently in clinical trials as the only treatment for NASH (Figure below right).
Figure (Below):
Histological samples were evaluated for steatosis, ballooning hepatocyte degeneration and inflammation. Steatosis is the build up of fat in the liver cells. This is largely unaffected by OCA or Aquamin. Ballooning degeneration is a form of liver cell death. This is reduced with OCA and even more by Aquamin. Inflammation is reduced by both compounds. The NAFLD a ctivity index is a summation of these 3 scores. Collagen deposition is the initial event triggering liver fibrosis. This is significantly reduced with Aquamin.
Figure (Below):
Non-alcoholic fatty liver disease (NAFLD) is highly prevalent globally. Fat accumulates in the liver usually due to unhealthy diets (Steatosis). When this fatty build up is followed by tissue inflammation and damage the disease is called non-alcoholic steatohepatitis (NASH). Aquamin prevents this disease progression.
