The effects of lauric acid and resveratrol intake on diet induced neuroinflammation, CD36 levels and cognitive behaviors of mice

The aim of this study was to examine the effects of lauric acid and resveratrol intake on high fat high fructose-induced neuroinflammation, anxiety and learning-related behaviors in mice and to determine the possible role of CD36 in these mechanisms. C57BL/6 (8 weeks old, male, n=31) mice were included in the study and divided into 4 groups. The control group was fed with standard rodent chow (10% kcal fat) and plain drinking water. The other three groups were fed high-fat feed (60% kcal fat) and fructose containing drinking water (5% w/v fructose) (HFFD). The second group only recieved HFFD (n=8) while in addition to HFFD, the third and fourth groups were given resveratrol (7,5 mg/kg, HFFD-RSV, n=7) or lauric acid (750 mg/kg, HFFDLA, n=8) by oral gavage. At the end of the intervention (6 weeks), inflammatory markers in plasma and brain tissues, CD36 levels, histopathology of the liver, body water, protein and fat ratios in animal carcasses were examined. Average energy intake with daily diet was higher in the HFFD, HFFD-RSV and HFFD-LA groups than the control group (p<0,05). The mean total body weight gain of the HFFD group was higher than the control group (p<0,05). The mean total body weight gain of the HFFD-RSV group was lower than the HFFD group (p<0,05). Total body fat ratio of the HFFD group was higher than that of the control group (p<0,05). Total body fat ratios of the HFFD-RSV and HFFD-LA groups were lower than the HFFD group (p<0,05). HFFD elicited anxiety-like behaviors, while HFFD-RSV and HFFDLA demonstrated improved anxiety-like behaviors (p<0,05). HFFD-LA led to a higher discrimination index than the other diet groups in the test measuring recognition memory (p<0,05). Brain and plasma GFAP and CD36 levels of the HFFD group were higher than the control group (p<0,05). Brain GFAP, CD36 and plasma CD36 levels were lower in the HFFDRSV group than the HFFD group (p<0,05). Brain GFAP, CD36 and plasma GFAP levels were lower in the HFFD-LA group than the HFFD group (p<0,05). Brain IL-6, MCP-1, IFN-γ, TNFα levels of the HFFD group were higher than the control group (p<0,05). Brain IL-6, MCP-1, IFN-γ, TNF-α levels were lower and IL-10 levels were higher in the HFFD-RSV group than the HFFD group (p<0,05). Brain MCP-1, IFN-γ, TNF-α levels were lower and IL-10 levels were higher in the HFFD-LA group than the HFFD group (p<0,05). Plasma IFN-γ, TNF-α, IL-12p70 levels were higher and IL-10 levels were lower of the HFFD group than the control group (p<0,05). Plasma IFN-γ, TNF-α, IL-12p70 levels were lower in the HFFD-RSV group than the HFFD group (p<0,05). Brain IFN-γ, TNF-α, IL-12p70 levels were lower and IL-10 levels were higher in the HFFD-LA group than the HFFD group (p<0,05). HFFD caused hepatocyte degeneration and microvesicular steatosis in the liver (p<0,05). HFFD-RSV and HFFD-LA reduced HFFD-induced hepatocyte degeneration and/or microvesicular steatosis in the liver (p<0,05). In conclusion, this study showed that supplementation of resveratrol and lauric acid reduced HFFD-induced obesity, neuroinflammation, systemic inflammation, anxiety-like behavior, hepatocyte degeneration, and microvesicular steatosis. Lauric acid has shown positive effects on cognitive performance. CD36 might be a potential biomarker for diet and neuroinflammation. The addition of dietary resveratrol and lauric acid sources in an adequate and balanced dietary pattern may improve health parameters associated with neuroinflammation. Key Words: Neuroinflammation, high fat diet, fructose, lauric acid, resveratrol, CD36