Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy

Abstract

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.

Krill oil prevents lipopolysaccharide-evoked acute liver injury in mice through inhibition of oxidative stress and inflammation

“…To characterize the inflammatory cell infiltration, immunohistochemistry (IHC) was performed with an F4/80 rabbit monoclonal antibody as described previously. 22 Briefly, the liver tissue sections were deparaffinized and rehydrated. The endogenous enzymes were blocked with 3% hydrogen peroxide.…”

“…To characterize the inflammatory cell infiltration, immunohistochemistry (IHC) was performed with an F4/80 rabbit monoclonal antibody as described previously. 22 Briefly, the…”

DHA-Enriched Phospholipids and EPA-Enriched Phospholipids Alleviate Lipopolysaccharide-Induced Intestinal Barrier Injury in Mice via a Sirtuin 1-Dependent Mechanism

“…Total RNA was isolated from ileum tissues using a RNAeasy animal RNA isolation kit with spin column (Beyotime Biotechnology). One microgram of RNA was reversed transcribed into cDNA, and then, the mRNA levels of target genes were determined by qRT-PCR according to our previous method . The sequences of primers used in this study are listed in Table S4.…”

“…After a 24 h fixation, ileum tissues were embedded in paraffin, cut into 4 μm thickness and then stained with hematoxylin and eosin (H&E). The immunohistochemical staining was carried out as described previously . Briefly, the sections of ileum were incubated with primary antibodies against claudin-1 (1:100 dilution), occludin (1:800 dilution), and ZO-1 (1:500 dilution) overnight at 4 °C, respectively.…”

Krill Oil Turns Off TGF-β1 Profibrotic Signaling in the Prevention of Diabetic Nephropathy

“…IHC staining was performed as described previously . The kidney sections were incubated overnight at 4 °C with antibodies against α-smooth muscle actin (α-SMA, 1:200, Proteintech, Wuhan, Hubei, China), collagen 1 α 1 (COL1A1, 1:200, Santa Cruz Biotechnology, Shanghai, China), interleukin 6 (IL-6, 1:200, Cell Signaling Technology, Shanghai, China), SMAD family member 7 (SMAD7, 1:100, Proteintech), and tumor necrosis factor α (TNF-α, 1:200, Santa Cruz Biotechnology).…”