Macrophage migration inhibitory factor deficiency aggravates effects of fructose-enriched diet on lipid metabolism in the mouse liver

Dietary fructose can disturb hepatic lipid metabolism in a way that leads to lipid accumulation and steatosis, which is often accompanied with low-grade inflammation. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of Mif deficiency in fructose-induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and Mif deficient (MIF-/-) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on hepatic lipid metabolism (both lipogenesis and beta-oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose-induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element-binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose-fed Mif deficient animals, and were most likely result of GR activation and facilitated uptake and decreased beta-oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that Mif deficiency aggravates the effects of energy-rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.

Automated summary

Dietary fructose can disturb hepatic lipid metabolism leading to lipid accumulation and steatosis, with Mif deficiency exacerbating these effects by enhancing inflammation and activating the GR signaling pathway.