Abstract 15294: Activation of Mac-1 Integrin Prevents G-CSF Mediated Monocyte Mobilization and Atherosclerosis Severity in Hypercholesterolemic Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sina Rahimpour ◽  
Annia Mesa ◽  
Lei Song ◽  
Natasha Fernandez ◽  
Si M Pham ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipid ◽  
High Fat ◽  
Once Daily ◽  
Leukocyte Mobilization ◽  
Sudan Iv ◽  
Low Levels ◽  
Atherosclerosis Development ◽  
Excessive Number ◽  
Atherosclerosis Severity

Background: Leukadherins (LA) are a novel family of Mac-1 agonists that increase cell adhesion and prevent leukocyte mobilization and tissue inflammation. This study brings new insights into how leukadherin LA1 protects hypercholesterolemic ApoE-null mice from excessive atherosclerosis development. Hypothesis: Activation of Mac-1 integrin with leukadherin LA1 retains monocytes in medullary and extramedullary centers and therefore, controls high fat diet induced monocytosis and atherosclerosis in ApoE-null mice. Methods and Results: Once daily administration of LA1 (10mg/kg) for 16 weeks significantly reduced atherosclerosis in the entire aorta and the aortic valve of high fat diet fed ApoE-null mice as determined by Sudan IV staining. The LA1 treatment had not effect on body weight or plasma lipid levels though it significantly reduced the number of circulating monocytes (Lin2- CD11c- CD11b+ by FACS). The remaining circulating monocytes in LA1-treated mice displayed low levels of Ly6C, a marker for inflammation. Interestingly, LA1 caused monocyte retention in the bone marrow (BM) and macrophages (F4/80+ by IHC) in the spleen of hypercholesterolemic mice, which account for the low numbers of monocytes seem in the circulation of these mice. On the other hand, the excessive number of BM monocytes didn’t compromise the number of hematopoietic (Lin- Sca+ c-Kit+) or myeloid (Lin- Sca- c-Kit+) progenitor cells. Finally, we assessed the effect of LA1 on systemic inflammatory mediators using multiplex immunoassay. The plasma levels of G-CSF, one of the main monocyte mobilization cytokines capable of promoting atherosclerosis in ApoE-null mice, were found reduced in a half in treated versus control mice. Conclusions: These data demonstrate that Mac-1 activation with LA1 significantly reduces atherosclerosis in hypercholesterolemic ApoE-null by impairing G-CSF mediated monocyte mobilization from medullary and extramedullary centers.

scholarly journals Olive Leaf Extract Attenuates Obesity in High-Fat Diet-Fed Mice by Modulating the Expression of Molecules Involved in Adipogenesis and Thermogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Shen ◽  
Su Jin Song ◽  
Narae Keum ◽  
Taesun Park
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Leaf Extract ◽  
Body Weight Gain ◽  
Plasma Lipid ◽  
Epididymal Adipose Tissue ◽  
Chow Diet ◽  
Olive Leaf ◽  
High Fat ◽  
Olive Leaf Extract

The present study aimed to investigate whether olive leaf extract (OLE) prevents high-fat diet (HFD)-induced obesity in mice and to explore the underlying mechanisms. Mice were randomly divided into groups that received a chow diet (CD), HFD, or 0.15% OLE-supplemented diet (OLD) for 8 weeks. OLD-fed mice showed significantly reduced body weight gain, visceral fat-pad weights, and plasma lipid levels as compared with HFD-fed mice. OLE significantly reversed the HFD-induced upregulation of WNT10b- and galanin-mediated signaling molecules and key adipogenic genes (PPARγ, C/EBPα, CD36, FAS, and leptin) in the epididymal adipose tissue of HFD-fed mice. Furthermore, the HFD-induced downregulation of thermogenic genes involved in uncoupled respiration (SIRT1, PGC1α, and UCP1) and mitochondrial biogenesis (TFAM, NRF-1, and COX2) was also significantly reversed by OLE. These results suggest that OLE exerts beneficial effects against obesity by regulating the expression of genes involved in adipogenesis and thermogenesis in the visceral adipose tissue of HFD-fed mice.

scholarly journals Associations Between Apolipoprotein-A5 Genotype, High-Fat Diet and Plasma Lipid Levels among HIV-infected Children Initiating Antiretroviral Therapy in India

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S216-S216 ◽  
Author(s):  
Ramalingam Srinivasan ◽  
Ramesh Karunaianantham ◽  
Padmapriyadarsini Chandrasekaran ◽  
Bindu Parachalil Gopalan ◽  
Sanjeeva G N ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
High Fat Diet ◽  
Plasma Lipid ◽  
Lipid Levels ◽  
High Fat ◽  
Apolipoprotein A5

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats

2019 ◽  
Vol 10 (8) ◽  
pp. 883-892
Author(s):  
L.C. Lew ◽  
Y.Y. Hor ◽  
M.H. Jaafar ◽  
A.S.Y. Lau ◽  
J.S. Ong ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Rat Model ◽  
High Fat Diet ◽  
Lactobacillus Reuteri ◽  
Plasma Lipid ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
High Fat ◽  
Age Related ◽  
Plasma Lipid Peroxidation

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5’adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

scholarly journals GPR55 Antagonist CID16020046 Protects against Atherosclerosis Development in Mice by Inhibiting Monocyte Adhesion and Mac-1 Expression

2021 ◽  
Vol 22 (23) ◽  
pp. 13084
Author(s):  
Seung-Jin Lee ◽  
Dong-Soon Im
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Monocyte Adhesion ◽  
High Fat ◽  
Potent Agonist ◽  
Atherosclerosis Development ◽  
Umbilical Vein Endothelial Cells

GPR55 recognizes several lipid molecules such as lysophosphatidylinositol. GPR55 expression was reported in human monocytes. However, its role in monocyte adhesion and atherosclerosis development has not been studied. The role of GPR55 in monocyte adhesion and atherosclerosis development was investigated in human THP-1 monocytes and ApoE−/− mice using O-1602 (a potent agonist of GPR55) and CID16020046 (a specific GPR55 antagonist). O-1602 treatment significantly increased monocyte adhesion to human umbilical vein endothelial cells, and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides −750 and −503 as GPR55 responsive elements. O-1602 induction of Mac-1 was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In Apo−/− mice, administration of CID16020046 ameliorated high-fat diet-induced atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to the adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis.

scholarly journals GPR55 antagonist CID16020046 protects against atherosclerosis development in mice by inhibiting monocyte adhesion and Mac-1 expression

2021 ◽  
Author(s):  
Seung-Jin Lee ◽  
DONG-SOON IM
Keyword(s):  
Endothelial Cells ◽  
High Fat Diet ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Monocyte Adhesion ◽  
High Fat ◽  
Atherosclerosis Development ◽  
Proinflammatory Role ◽  
Umbilical Vein Endothelial Cells

Background and Purpose: GPR55 is a G protein-coupled receptor that recognizes several lipid molecules. GPR55 expression in human monocytes and its proinflammatory role lead us to investigate the role of GPR55 in monocyte adhesion and atherosclerosis development. Experimental Approach: We investigated monocyte adhesion in human THP-1 monocytes and atherosclerosis development in ApoE-/- mice by using O-1602 (a potent agonist of GPR55), CID16020046 (a specific GPR55 antagonist), and a high-fat diet-induced atherosclerosis model. Key Results: In human THP-1 monocytes, treatment with O-1602 significantly increased monocyte adhesion to human umbilical vein endothelial cells (HUVECs), and the O-1602-induced adhesion was inhibited by treatment with CID16020046. O-1602 induced the expression of Mac-1 adhesion molecules, whereas CID16020046 inhibited this induction. Analysis of the promoter region of Mac-1 elucidated the binding sites of AP-1 and NF-κB between nucleotides -750 and -503 as GPR55 responsive elements. Furthermore, O-1602 induction of Mac-1 through AP-1 and NF-B was found to be dependent on the signaling components of GPR55, that is, Gq protein, Ca2+, CaMKK, and PI3K. In an in vivo study of high-fat diet-induced atherosclerosis in ApoE-/- mice, administration of CID16020046 ameliorated atherosclerosis development. These results suggest that high-fat diet-induced GPR55 activation leads to adhesion of monocytes to endothelial cells via induction of Mac-1, and CID16020046 blockage of GPR55 could suppress monocyte adhesion to vascular endothelial cells through suppression of Mac-1 expression, leading to protection against the development of atherosclerosis. Conclusions: This report suggests that GPR55 may be a therapeutic target for atherosclerosis development.

scholarly journals The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenyun Zeng ◽  
Danbin Wu ◽  
Yingxin Sun ◽  
Yanrong Suo ◽  
Qun Yu ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
In Vitro Study ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
High Fat ◽  
Nlrp3 Inflammasome Activation ◽  
Atherosclerosis Development

AbstractNLRP3 inflammasome is a vital player in macrophages pyroptosis, which is a type of proinflammatory cell-death and takes part in the pathogenesis of atherosclerosis. In this study, we used apoE−/− mice and ox-LDL induced THP-1 derived macrophages to explore the mechanisms of MCC950, a selective NLRP3 inhibitor in treating atherosclerosis. For the in vivo study, MCC950 was intraperitoneal injected to 8-week-old apoE−/− mice fed with high-fat diet for 12 weeks. For the in vitro study, THP-1 derived macrophages were treated with ox-LDL and MCC950 for 48 h. MCC950 administration reduced plaque areas and macrophages contents, but did not improve the serum lipid profiles in aortic root of apoE−/− mice. MCC950 inhibited the activation of NLRP3/ASC/Caspase-1/GSDMD-N axis, and alleviated macrophages pyroptosis and the production of IL-1β and IL-18 both in aorta and in cell lysates. However, MCC950 did not affect the expression of TLR4 or the mRNA levels of NLRP3 inflammasome and its downstream proteins, suggesting that MCC950 had no effects on the priming of NLRP3 inflammasome activation in macrophages. The anti-atherosclerotic mechanisms of MCC950 on attenuating macrophages inflammation and pyroptosis involved in inhibiting the assembly and activation of NLRP3 inflammasome, rather than interrupting its priming.

Abstract 128: Short-Term, High-Saturated and Trans Fatty Acid Diet Increases Expression of Key Intestinal Genes Involved in Lipoprotein Metabolism in Healthy Males

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
André J Tremblay ◽  
Benoit Lamarche ◽  
Valerie Guay ◽  
Valery Lemelin ◽  
Patrick Couture
Keyword(s):  
Fatty Acids ◽  
Apolipoprotein B ◽  
High Fat Diet ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
High Fat ◽  
Low Fat ◽  
Short Term ◽  
Low Fat Diet ◽  
Key Genes

Dietary saturated fat (SFA) and trans fatty acids (TFA) have been linked to an increased risk of cardiovascular disease mainly by increasing plasma LDL-C levels. The modulation of cholesterol and fatty acids homeostasis by SFA and TFA is thought to be mediated by changes in expression of key intestinal genes involved in lipid and lipoprotein metabolism. However, the short-term impact of dietary fat intake on expression of these genes has not been fully investigated. To test whether short-term changes in SFA and TFA intake affects expression of key intestinal genes involved in lipid and lipoprotein metabolism, we conducted a randomized, double-blind, cross-over study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: 1) high-fat diet (37% energy from fat, 15% from SFA, 3.5% from TFA and 50% energy from carbohydrate) and 2) low-fat diet (25% energy from fat, 6% from SFA, 0% from TFA and 62% energy from carbohydrate) in random order, each separated by a two-week washout period. Fasting plasma lipid levels were determined and expression of key genes involved in lipid and lipoprotein metabolism was compared by real-time PCR quantification in duodenal biopsy specimens obtained in the fasted state after 3 days of feeding on each diet. Following the 3-day high-fat diet, plasma-C (+7.4%, P=0.02), LDL-C (+16.9%, P=0.005) and HDL-C (+9.3%, P=0.002) levels were significantly increased as compared to low-fat diet. Plasma triglycerides (-31.7%, P=0.001) and apolipoprotein B-48 (-39.6%, P=0.003) levels were significantly decreased after the high-fat diet relative to the low-fat diet. The high-fat diet also resulted in significant increases in intestinal mRNA expression levels of SREBP-2, HNF-4α, PPAR-α, PPAR-γ, NPC1L1, ABCG8, FABP-2, ACAC-α, SCD-1, ELOVL5, DGAT-2, apolipoprotein B, MTTP, SAR1β and LDL receptor. These findings suggest that short-term exposure to a high-SFA and TFA diet upregulates the expression of key genes involved in lipid and lipoprotein metabolism at the enterocyte level.

Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats

2013 ◽  
Vol 38 (8) ◽  
pp. 836-843 ◽  
Author(s):  
Tianrun Li ◽  
Leiluo Geng ◽  
Xin Chen ◽  
Miranda Miskowiec ◽  
Xuan Li ◽  
...  
Keyword(s):  
Amino Acids ◽  
Blood Flow ◽  
High Fat Diet ◽  
Plasma Lipid ◽  
Branched Chain Amino Acids ◽  
Fat Deposition ◽  
The Body ◽  
High Fat ◽  
Branched Chain ◽  
Rat Livers

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.

scholarly journals Marine n-3 fatty acids promote size reduction of visceral adipose depots, without altering body weight and composition, in male Wistar rats fed a high-fat diet

2009 ◽  
Vol 102 (7) ◽  
pp. 995-1006 ◽  
Author(s):  
Merethe H. Rokling-Andersen ◽  
Arild C. Rustan ◽  
Andreas J. Wensaas ◽  
Olav Kaalhus ◽  
Hege Wergedahl ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Plasma Lipid ◽  
Feed Consumption ◽  
High Fat ◽  
Male Wistar Rats ◽  
Similar Body ◽  
Visceral Adipose

We evaluated the effects of partly substituting lard with marine n-3 fatty acids (FA) on body composition and weight, adipose tissue distribution and gene expression in five adipose depots of male Wistar rats fed a high-fat diet. Rats were fed diets including lard (19·5 % lard) or n-3 FA (9·1 % lard and 10·4 % Triomar™) for 7 weeks. Feed consumption and weight gain were similar, whereas plasma lipid concentrations were lower in the n-3 FA group. Magnetic resonance imaging revealed smaller visceral (mesenteric, perirenal and epididymal) adipose depots in the n-3 FA-fed animals (35, 44 and 32 % reductions, respectively). n-3 FA feeding increased mRNA expression of cytokines as well as chemokines in several adipose depots. Expression of Adipoq and Pparg was enhanced in the mesenteric adipose depots of the n-3 FA-fed rats, and fasting plasma insulin levels were lowered. Expression of the lipogenic enzymes Acaca and Fasn was increased in the visceral adipose depots, whereas Dgat1 was reduced in the perirenal and epididymal depots. Cpt2 mRNA expression was almost doubled in the mesenteric depot and liver. Carcass analyses showed similar body fat (%) in the two feeding groups, indicating that n-3 FA feeding led to redistribution of fat away from the visceral compartment.

Sign in / Sign up

Export Citation Format

Share Document