Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.

Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degen- eration in Raw 264.7 cells involving the AMPK/SREBP1 pathway

Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.

A novel rat model of fatty organ degeneration induced by poloxamer 407

Traditional methods of inducing hyperlipidemia in animal models are either costly(genetic manipulation)or it is difficult to control for the effects of other variables.For example,during high-fat feeding,the amount of high-fat diet intake per animal cannot be precisely controlled.The aim of this study was to develop an experimental model of fatty organ degeneration induced by poloxamer 407(P-407).The study was conducted in 2-month-old,male Sprague-Dawley rats that were administered intraperitoneally with either 10%(w/w)P-407(1 g/kg)or saline(10 mL/kg)for 4 months.Their lipid profile,organ degeneration due to fat deposition,and body mass were assessed.Intraperitoneal administration of P-407 resulted in significant increases in plasma triglycerides(P
0.001),total cholesterol(P<0.001),high-density lipoprotein-cholesterol(P
0.001),and low-density lipoprotein(P<0.001)cholesterol.In contrast to the control group,fatty tissue degeneration was observed in the liver,spleen,and kidneys of P-407-treated rats.Positive correlations between fatty tissue degeneration,and the atherogenic index of plasma(P<0.001)and the ratio of total cholesterol to high-density-lipoprotein(P<0.001)were identified.In addition,treatment with P-407 for 3 to 4 months caused a significant reduction in body mass relative to controls(P<0.001).Thus,this study describes the development of a cost-effective experimental rat model of organ degeneration,characterized by fat accumulation in the liver,spleen,and kidneys,which could be used for the study of steatosis and related diseases arising from sustained untreated dyslipidemia.Furthermore,both the atherogenic index of plasma and the ratio of total cholesterol to high-density lipoprotein-cholesterol can be used to predict the risk of fatty tissue degeneration in this model.The study was approval of the University of Jishou Biomedical Research Ethics Committee,China.