Amino Acid Citrulline Mitigates Non-Alcoholic Fatty Liver Disease Associated with Western Diet

by | Sep 11, 2018 | 2016, Amino Acids, Citrulline, Liver Health

Written by Angeline A. De Leon, Staff Writer. Using a rat model researchers demonstrate that supplementation with amino acid citrulline may help mitigate liver injury induced by a western diet.

Nonalcoholic fatty liver disease (NAFLD), now reaching epidemic proportions, is currently the most common cause of chronic liver disease worldwide, with a prevalence of 25%‐30% of the general population. According to recent estimates, 64 million people may have NAFLD in the United States while Europe has an estimated 53 million affected individuals. These figures point to a daunting and enormous disease burden of NAFLD that is closely related to the obesity epidemic and has an impact on mortality as patients with NAFLD exhibit an increased risk of death compared to the general population.1

The Western Diet (Standard American Diet) is characterized by high intake of red meats, saturated fat, “empty” carbohydrates, and prepackaged foods and low intake of fresh fruits and vegetables and whole grains. This modern dietary pattern has been linked to a number of diseases, and in the context of metabolic syndrome, such a high-fat, high-fructose diet has been shown to induce insulin resistance and visceral fat accumulation 1, known risk factors for non-alcoholic fatty liver disease (NAFLD) 2. NAFLD is the most common type of chronic liver disease and if left untreated, can progress to nonalcoholic steatohepatitis (NASH) which, along with severe fat accumulation in the liver, involves inflammation and liver cell damage 3. Research on NAFLD and NASH has concluded that proper management of lipid metabolism and inflammatory processes are crucial to prevention and/or mitigation of disease, with treatments primarily targeting intestinal microbiota and gut barrier function 4. One form of treatment, protein or amino acid supplementation, specifically shows the ability to improve steatosis (buildup of fat in liver) by modulating lipid metabolism, insulin sensitivity, and glucose tolerance 5,6. The amino acid citrulline (Cit), known to regulate protein and energy metabolism, appears to influence microbiota composition in the large intestine 7 and has been shown to improve intestinal permeability and mitigate intestinal inflammation in animal models 8. Initial studies also support the capacity of Cit to improve hepatic lipid metabolism and steatosis 9. In a recent study published in the British Journal of Nutrition (2016), researchers in France assessed whether supplementation with Cit could improve liver and gut function in a rat model of NAFLD induced by a Western Diet.

A total of 43 6-week-old male Sprague-Dawley rats were randomly assigned to one of four groups, receiving a standard rodent chow (C), a Western diet (WD, involving 45% fat and 30% fructose in drinking water), a Western diet supplemented with non-essential amino acids (WDA), or a Western diet supplemented with 1 g/kg Cit (WDC) daily for eight weeks. Animals received food and drinks ad libitum and 24h urine samples were collected. Following the feeding period and after an overnight fast, rats were sacrificed and blood samples and liver and gut samples were obtained for analysis of hepatic steatosis, inflammation, and metabolic markers. Samples of colon mucosa were also collected to determine gut microbiota.

Analyses revealed the following key findings:

  • In comparison to control, WD and WDA rats had higher levels of visceral fat (p = 0.003 and p = 0.002, respectively) and lower levels of lean mass (p < 0.05 for both). Western diet-fed rats also showed higher plasma triglycerides (TAG) (p < 0.05), cholesterol (p < 0.01), insulin (p < 0.05), and glucose (p < 0.001), in comparison to control rats.
  • Compared to the WD group, rats receiving non-essential amino acids and Cit showed significantly lower plasma TAG (39% and 32%, respectively, p < 0.05) and plasma insulin (p < 0.05 for both).
  • In comparison to the WD group, Cit supplementation also resulted in lower liver weight (p < 0.05) and was associated with lower mRNA expression of pro-inflammatory cytokines IL6, Tnfα, and Tl4r (p < 0.05 for all). Cit also reduced Tnfα and Tl4r expression in the colon (p < 0.05 for both) and increased claudin-1 protein expression (marker of gut health associated with intestinal barrier function) (p = 0.02).

Overall, evidence from the study confirms the negative effects of a Western diet on liver and gut function and suggests that supplementation with amino acid citrulline may help mitigate liver injury. Through reduced lipid accumulation, increased insulin sensitivity, and decreased inflammation (both at the liver and gut level), severity of steatosis may be reduced and progression of NAFLD to NASH may be possible with citrulline. Replication of findings in human subjects would be an important next step.

Source: Jegatheesan P, Beutheu S, Freese K, et al. Preventative effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats. British Journal of Nutrition. 2016; 116: 191-203. DOI: 10.1017/S0007114516001793.

© The Authors 2016 Open Access

Click here to read the full text study.

Posted September 11, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

 

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