lactoferrin and Fatty-Liver

Topics: Animals; Aorta; Atherosclerosis; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Diet, High-Fat; Fatty Liver; Homeostasis; Intestine, Small; Lactoferrin; Lipid Metabolism; Liver; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE

Lactoferrin was reported to exert modulatory effects on lipid metabolism, but the regulatory mechanisms remain unclear. The present study investigated the beneficial effects of lactoferrin and their underlying mechanisms in high-fat diet-induced obese C57BL/6J mice. Oral administration of lactoferrin at 100 mg per body weight for 15 weeks significantly reduced weight gain, visceral adiposity, and serum glucose, leptin, and lipid levels in high-fat diet-induced obese mice. Hepatic steatosis in the obese mice was significantly improved. Expression of adipogenic and inflammation-related genes and proteins (SREBP-1c, FAS, MCP-1, leptin) was suppressed in the liver and epididymal adipose tissue of the obese mice. The present findings demonstrate that lactoferrin positively regulated lipid metabolism and improved hepatic steatosis in obese mice. The mechanisms of action for these effects may be attributed to suppression of lipogenic gene expression and amelioration of inflammation in the liver and epididymal adipose tissue.

Topics: Animals; Chemokine CCL2; Diet, High-Fat; Down-Regulation; Fatty Liver; Humans; Lactoferrin; Lipid Metabolism; Lipogenesis; Liver; Male; Mice; Mice, Inbred C57BL; Sterol Regulatory Element Binding Protein 1

Polyethylene glycol (PEG) is attached to proteins in order to increase their half-life in circulation and reduce their immunogenicity in vivo. The present study was conducted to examine whether two different sizes of PEGylated bovine lactoferrin (40k-PEG-bLf and 20k-PEG-bLf) would enhance the protective effect of native bLf on liver injury induced by carbon tetrachloride (CCl(4)) in rats. Silymarin, a known hepatoprotective drug was used as a positive control. Compared to native bLf, the treatment of PEGylated bLf more markedly prevented the elevation of serum levels of hepatic enzyme markers and inhibited fatty degeneration and the hepatic necrosis induced by CCl(4). 40k-PEG-bLf showed a more significant suppressive effect on CCl(4)-induced hepatic injury than 20k-PEG-bLf. The treatment with PEGylated bLf elevated serum SOD activity reduced by CCl(4) more significantly than native bLf. 40k-PEG-bLf enhanced serum SOD activity more significantly than 20k-PEG-bLf. Immunohistochemical study showed that the PEGylation of bLf enhanced its intracellular transportation to hepatocytes. The increases in intracellular transportation of the PEGylated bLf in order were: 40k-PEG-bLf>20k-PEG-bLf>native bLf. These findings suggested that the mechanism of the enhancement of hepatoprotective effect by PEGylated bLf was associated with an increase in the intracellular transportation of PEGylated bLf in hepatocytes.

Topics: Animals; Apoptosis; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Fatty Liver; Hepatocytes; Immunohistochemistry; Lactoferrin; Lipid Peroxidation; Liver; Male; Necrosis; Polyethylene Glycols; Protective Agents; Rats; Rats, Wistar; Silymarin; Superoxide Dismutase