Inflammatory stress induces lipid accumulation in multi-organs of db/db mice.
Dyslipidemia and chronic inflammation play crucial roles in the progression of diabetes. This study aimed to investigate the effects of inflammatory stress on lipid accumulation in multi-organs in diabetes. Eight-week-old male db/db mice were randomly assigned to inflamed group with alternating day subcutaneous injection of 10% casein or control group with daily injection of distilled water. The lipid profile and plasma levels of inflammatory cytokines were determined using a clinical biochemical assay and enzyme-linked immunosorbent assay. The effects of inflammation on lipid accumulation in target organs were evaluated by hematoxylin-eosin staining, Oil Red O staining, Filipin staining, and a quantitative intracellular cholesterol assay. The protein expressions of low-density lipoprotein receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2), and SREBP-cleavage-activating protein (SCAP) in tissues were assessed by immunohistochemical staining and western blotting. Results showed that the serum levels of inflammatory cytokines were significantly elevated in casein-injected mice, suggesting that an inflamed diabetic model was established. Furthermore, the protein expressions of inflammatory cytokines in aortas, livers, kidneys, and intestines were significantly increased in inflamed group compared with control. Whereas the serum levels of lipid moieties in inflamed mice were not different compared with the control, inflammatory stress significantly increased lipid accumulation in aortas, livers, kidneys, and intestines, which coincided with increased protein expressions of LDLr, SREBP-2, and SCAP in these organs of inflamed mice. In conclusion, inflammation induces lipid accumulation in multi-organs of db/db mice from the circulation to peripheral tissues, potentially due to lipid redistribution mediated by the disruption of LDLr feedback regulation.
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China klma05@163.com.
Kun Ling
KL
Ma
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Yang
Y
Zhang
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Jing
J
Liu
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Yu
Y
Wu
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Ze Bo
ZB
Hu
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Liang
L
Liu
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Bi Cheng
BC
Liu
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D048909:Diabetes Complications / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008055:Lipids / Q000276:immunology*; D008297:Male; D008815:Mice, Inbred Strains; D009928:Organ Specificity / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology*; D014018:Tissue Distribution; D014781:Viscera / Q000276:immunology*
D016207:Cytokines; D008055:Lipids
LDL receptor; diabetes; inflammatory stress; lipid accumulation; lipid redistribution