New research shows that amino acids are the main carbon source of liver fat, and long-term excessive intake may increase the burden on the liver.
Carbohydrates have historically been considered the main driver of new fat in the liver, but the conversion of glucose or fructose to fatty acids in the liver is inexplicably low.
In a new study, the authors found that labeled glucose in the diet contributes the least to new fat in the liver compared to other tissues.
Using the National Health and Nutrition Examination Survey (NHANES) dataset, the authors found that, contrary to popular belief, it is low-carb water intake, not high-carb water intake, that promotes liver fat accumulation.
Further, the dataset showed that high protein intake increased the risk of fatty liver disease.
These results suggest a previously underappreciated role of dietary protein in fat accumulation in the liver.
This may be related to the metabolic characteristics of the liver. Animal liver is the main site of amino acid metabolism, and the enrichment degree of amino acid metabolism genes in liver is much higher than that of glycolysis genes.
The tricarboxylic acid cycle (TCA) can provide energy and carbon source for anabolic pathway, and is the hub of energy metabolism and substance metabolism.
In the liver, amino acids rather than glucose are the primary substrate for oxidative phosphorylation, and TCA is more dependent on amino acids as feedstock for energy and carbon sources.
Therefore, citric acid, which is associated with glucose metabolism in the liver, may withdraw from TCA, which in turn provides energy and raw materials for fat metabolism.
To test this hypothesis, the authors performed a side-by-side comparative analysis of glucose and glutamine-synthesizing triglyceride fluxes in primary hepatocytes isolated from fed wild-type mice.
Consistent with the hypothesis, glutamine rather than glucose-derived C-13 is more readily converted to palmitic acid in liver cells.
The incorporation efficiency of glutamine and other amino acids is 14 and 8 times that of glucose, respectively.
Overall, glutamine is 8 to 40 times more potent as a carbon source for fat synthesis than glucose.
In previous feasibility studies involving reduced-protein feeds, more attention has been paid to cost, environment, and the effects of undegraded proteins on allergy or microbial homeostasis.
This new study suggests that we also need to pay attention to the effects of high-protein diet on liver and energy metabolism from the physiological characteristics of liver metabolism.
It is not difficult to see that this metabolic characteristic of the liver may be related to the role of the liver in gluconeogenesis.
Due to the need for gluconeogenesis, the liver needs adequate amino acid metabolism as support.
This infrastructure is likely to be exploited by the large supply of protein, leading to excessive accumulation of sugars and lipids.
If this condition persists for a long time, it may cause insulin resistance and lead to serious metabolic disorders.
The study also suggests that supplementation of non-essential amino acids, especially glutamine, may be necessary when the liver is dealing with detoxification and stress.
Overall, it is necessary to reduce the protein in the feed.
At the same time, the addition of amino acids may need to consider more factors, such as stress and detoxification, the body’s demand for amino acids may be completely different from normal conditions.
