Characterization of coconut oil and CLA induced lipolysis

Obesity is a main health concern and leads to many other health complications. Conjugated linoleic acid (CLA) has been shown to cause a reduction in obesity in several species. CLAinduced body fat loss is enhanced when mice are fed coconut oil (CO). The objectives were to determine if the CLA-induced lipolysis in different oil source-fed mice was time-dependent and to determine the effect of cell signaling inhibitors on CO+CLA-induced lipolysis. Study 1: Male mice (ICR; n=80; 3wk) were fed 7% soybean oil (SO) or CO diets for 6wk and then supplemented with 0 or 0.5% CLA for 3, 7, 10 or 14d. Body fat index (BFI) was calculated as [(epididymal fat pad + retroperitoneal fat pad)/ body weight] and lipolysis was determined by non-esterified fatty acid (NEFA) and glycerol release in 3hr ex vivo cultures. BFI was reduced by CO on d7 (P\u3c0.01) and CLA tended (P=0.09) to decrease BFI in CO-fed mice on d10. BFI was reduced in both CO and SO-fed mice (P\u3c0.05) in response to CLA on d14. NEFA release was increased by CLA in CO-fed mice (P\u3c0.01) but not in SO-fed mice on d7 and 10 but on d14 CLA increased NEFA release in both CO and SO-fed mice (P\u3c0.0001). Glycerol release was also increased by CLA in CO-fed mice but not in SO-fed mice on d3 and d7 (P\u3c0.05). We then determined expression and activation level of proteins involved in lipolysis and lipogenesis. CLA tended to decrease (P=0.06) p-perilipin protein expression in CO-fed mice. There was also a trend for CLA (P=0.06) to decrease adipose triglyceride lipase (ATGL) protein. CO-fed mice had greater fatty acid synthase, stearoyl CoA desaturase 1 mRNA expression and less acetyl CoA carboxylase mRNA expression (P\u3c0.01). Sterol regulatory binding protein 1c and malic enzyme expression was least in CO+CLA-fed mice. Study 2: 3T3-L1 cells were differentiated, exposed to CO or SO for 10d, serum starved overnight, and pre-loaded with 3[H]-oleic acid for 12 hrs. Cells were treated with 50 muM CLA or linoleic acid (LA) with/without cell signaling inhibitors for 12-24 hrs. Lipolysis was measured as the 3-hr release of 3[H]-oleic acid. Without inhibitors, CO+CLA treatment caused more lipolysis (P\u3c0.01) than all other treatments, which did not differ. None of the inhibitors tested reduced lipolysis in CO+CLA treated cells. Cyclooxegenase-2 inhibitor increased lipolysis of SO+CLA treated cells (P=0.05) to the level of CO+CLA. Phospholipase C inhibitor increased lipolysis in all treatments (P\u3c0.0001) except that of CO+CLA. Peroxisome proliferator-activated receptor alpha inhibitor also increased lipolysis of CO+LA (P\u3c0.05) to the level of CO+CLA treated cells and in SO+CLA treated cells. There was no effect of the p42 mitogen-activated protein kinase or protein kinase A inhibitor, compared to absence of inhibitor. Therefore CLA-induced lipolysis occurs more rapidly in CO vs SO-fed mice and the CLA enhanced lipolysis in CO group could involve the PLC pathway

Coconut oil enhancement of conjugated linoleic acid induced body fat loss and lipolysis in mice

Dietary conjugated linoleic acid (CLA) causes a body fat loss that is enhanced when mice are fed coconut oil (CO) compared to soy oil (SO). The objectives were to determine if CLA feeding altered proteins involved in lipolysis. Male mice (n = 80; 3 wk old) were fed 7% SO or CO diets for 6 wk then 0 or 0.5% CLA for 12d. A body fat index was calculated: (retroperitoneal (RP) + epididymal (EPI) fat pads)*100/body weight. Lipolysis was determined by non-esterified fatty acid (NEFA) and glycerol release from EPI & RP explants. The relative expression of perilipin, phosphorylated perilipin (P-perilipin), hormone sensitive lipase (HSL), phosphorylated HSL (P-HSL), adipocyte triglyceride lipase (ATGL), and adipocyte differentiation related protein (ADRP) were determined by western blotting. The body fat index was reduced by both CLA (P \u3c 0.05) and CO (P \u3c 0.001) but there was no interaction. NEFA release was increased by CLA in CO-fed mice (2.94 and 8.63 mumol/g; P \u3c 0.05) but not in SO-fed mice (1.76 vs 2.26 mumol/g tissue). Glycerol release was not affected by CO or CLA. Total perilipin had a main effect of oil source, where it was decreased by CO feeding (P \u3c 0.05) but P-perilipin tended to be increased by CLA in SO-fed mice and decreased by CLA in CO-fed mice (P = 0.08). HSL expression had a main effect of oil source where CO feeding decreased the expression (P \u3c 0.05), but P-HSL expression wasn\u27t affected by diet. ATGL expression had a main effect of oil source, it was decreased by CO feeding (P \u3c 0.01) but wasn\u27t altered by CLA. This may indicate that the CLA-stimulated lipolysis in CO-fed mice is on the decline since P-perilipin, and P-HSL are associated with increased lipase activity. ADRP expression wasn\u27t affected by any diet, suggesting that there is no significant de-differentiation of adipocytes in vivo. In conclusion coconut oil enhances the anti-obesity effect of CLA and this effect is, at least in part, due to enhanced lipolysis

RAGE limits regeneration after massive liver injury by coordinated suppression of TNF-α and NF-κB

The exquisite ability of the liver to regenerate is finite. Identification of mechanisms that limit regeneration after massive injury holds the key to expanding the limits of liver transplantation and salvaging livers and hosts overwhelmed by carcinoma and toxic insults. Receptor for advanced glycation endproducts (RAGE) is up-regulated in liver remnants selectively after massive (85%) versus partial (70%) hepatectomy, principally in mononuclear phagocyte-derived dendritic cells (MPDDCs). Blockade of RAGE, using pharmacological antagonists or transgenic mice in which a signaling-deficient RAGE mutant is expressed in cells of mononuclear phagocyte lineage, significantly increases survival after massive liver resection. In the first hours after massive resection, remnants retrieved from RAGE-blocked mice displayed increased activated NF-κB, principally in hepatocytes, and enhanced expression of regeneration-promoting cytokines, TNF-α and IL-6, and the antiinflammatory cytokine, IL-10. Hepatocyte proliferation was increased by RAGE blockade, in parallel with significantly reduced apoptosis. These data highlight central roles for RAGE and MPDDCs in modulation of cell death–promoting mechanisms in massive hepatectomy and suggest that RAGE blockade is a novel strategy to promote regeneration in the massively injured liver

Mrp1 is involved in lipid presentation and iNKT cell activation by Streptococcus pneumoniae

The CD1d pathway present lipid antigens resulting in the activation of iNKT cells but the complete pathway remains to be fully elucidated. Here, Chandra et al. use an siRNA screen and identify Mrp1 as crucial for CD1d lipid presentation and activation of iNKT in the context of Streptococcus pneumoniae infection

IL-17 in the immunopathogenesis of spondyloarthritis

pondyloarthritis (SpA) is a term that refers to a group of inflammatory diseases that includes psoriatic arthritis, axial SpA and nonradiographic axial SpA, reactive arthritis, enteropathic arthritis and undifferentiated SpA. The disease subtypes share clinical and immunological features, including joint inflammation (peripheral and axial skeleton); skin, gut and eye manifestations; and the absence of diagnostic autoantibodies (seronegative). The diseases also share genetic factors. The aetiology of SpA is still the subject of research by many groups worldwide. Evidence from genetic, experimental and clinical studies has accumulated to indicate a clear role for the IL-17 pathway in the pathogenesis of SpA. The IL-17 family consists of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F, of which IL-17A is the best studied. IL-17A is a pro-inflammatory cytokine that also has the capacity to promote angiogenesis and osteoclastogenesis. Of the six family members, IL-17A has the strongest homology with IL-17F. In this Review, we discuss how IL-17A and IL-17F and their cellular sources might contribute to the immunopathology of SpA