Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor

Tran, Deanna; Tran, Diana; Mattai, S. Anjani; Sallam, Tamer; Ortiz, Christina; Lee, E C; Robbins, Lori; Ho, Samantha; Lee, J E; Fisseha, E.; Shieh, Christine; Sideri, Aristea; Shih, David Q.; Fleshner, Phillip; McGovern, D P B; Vu, Michelle; Hing, Tressia; Bakirtzi, Kyriaki; Cheng, Michelle; Su, Bowei; Law, Ivy Ka Man; Καραγιαννίδης, Ιορδάνης; Targan, Stephan R.; Gallo, Richard L.; Li, Z; Koon, Hon Wai

doi:10.1038/ijo.2016.90

Cited by 37 publications

(36 citation statements)

References 39 publications

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“…Our data demonstrate that exogenous CRAMP administration reduces alcohol-induced hepatic steatosis, which is in line with previous research showing that lentivirus-mediated CRAMP overexpression reduced hepatic fat accumulation in obese subjects [49]. We further demonstrated that CRAMP peptide reduces alcoholinduced LPS and inflammasome activation by decreasing hepatic Lbp and Cd14 expression and UA production.…”

Section: Cramp Alleviates Alcoholic Liver Disease 379supporting

confidence: 92%

Cathelicidin‐related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation

Zhao

Shao

et al. 2020

The Journal of Pathology

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Alcoholic liver disease (ALD) is associated with gut dysbiosis and hepatic inflammasome activation. While it is known that antimicrobial peptides (AMPs) play a critical role in the regulation of bacterial homeostasis in ALD, the functional role of AMPs in the alcohol-induced inflammasome activation is unclear. The aim of this study was to determine the effects of cathelicidin-related antimicrobial peptide (CRAMP) on inflammasome activation in ALD. CRAMP knockout (Camp −/−) and wild-type (WT) mice were subjected to binge-on-chronic alcohol feeding and synthetic CRAMP peptide was administered. Serum/plasma and hepatic tissue samples from human subjects with alcohol use disorder and/or alcoholic hepatitis were analyzed. CRAMP deficiency exacerbated ALD with enhanced inflammasome activation as shown by elevated serum interleukin (IL)-1β levels. Although Camp −/− mice had comparable serum endotoxin levels compared to WT mice after alcohol feeding, hepatic lipopolysaccharide (LPS) binding protein (LBP) and cluster of differentiation (CD) 14 were increased. Serum levels of uric acid (UA), a Signal 2 molecule in inflammasome activation, were positively correlated with serum levels of IL-1β in alcohol use disorder patients with ALD and were increased in Camp −/− mice fed alcohol. In vitro studies showed that CRAMP peptide inhibited LPS binding to macrophages and inflammasome activation stimulated by a combination of LPS and UA. Synthetic CRAMP peptide administration decreased serum UA and IL-1β concentrations and rescued the liver from alcohol-induced damage in both WT and Camp −/− mice. In summary, CRAMP exhibited a protective role against binge-on-chronic alcohol-induced liver damage via regulation of inflammasome activation by decreasing LPS binding and UA production. CRAMP administration may represent a novel strategy for treating ALD.

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Section: Cramp Alleviates Alcoholic Liver Disease 379supporting

confidence: 92%

Cathelicidin‐related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation

Zhao

Shao

et al. 2020

The Journal of Pathology

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“…A meta-analysis found that the CD36 gene was significantly linked to triglycerides and triglycerides/HDL-C ratio but not linked to LDL or total cholesterol [ 32 ]. In addition, many studies have demonstrated that the polymorphism of CD36 influences the serum lipid levels in the patients of atherosclerosis, coronary heart disease, and metabolic syndrome [ 33 – 35 ]. Importantly, as the Rotterdam Study found, low serum triglycerides levels were also associated with an increased risk of ICH [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

CD36 Gene Polymorphisms Are Associated with Intracerebral Hemorrhage Susceptibility in a Han Chinese Population

Gong

Liao

Liu

et al. 2017

BioMed Research International

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The CD36 gene encodes a membrane glycoprotein (type B scavenger receptor, SR-B2) that plays a crucial role in lipid sensing, innate immunity, atherogenesis, and glycolipid metabolism. In this study, we aimed to investigate the association between CD36 gene polymorphisms and intracerebral hemorrhage (ICH) in a Han Chinese population. We performed genotype and allele analyses for eleven single nucleotide polymorphisms (SNPs) of CD36 in a case-controlled study involving 292 ICH patients and 298 control participants. Eleven SNPs were genotyped by the Improved Multiple Ligase Detection Reaction (iMLDR) method. The results indicated that the SNP rs1194182 values were significantly different between ICH group and control group in a dominant model after adjusting for confounding factors. The subgroup analysis conducted for rs1194182 showed that the allele G frequencies were significantly different between ICH patients and controls in hypertension group via a dominant model. We then analyzed the rs1194182 genotype distributions among different groups of the serum lipid groups, including BMI, TC, TG, HDL, and LDL. However, no significant differences were found in the analysis of other subgroups. Taken together, these findings indicate that rs1194182 polymorphism in the CD36 gene was associated with ICH, and genotype GG could be an independent predictor.

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“…Hoang-Yen Tran et al have found that obese non-diabetic patients have higher levels of cathelicidin LL-37 compared with patients with normal BMI. Even in comparison with obese prediabetic patients, obese non-diabetic patients had increased serum LL-37 concentrations 35 . Additionally, this group has found that LL-37 inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to reduction of hepatic steatosis and fat mass.…”

Section: Discussionmentioning

confidence: 89%

“…Data on the influence of body composition on LL-37 expression are still incomplete. There are studies showing that there is an association between metabolic parameters (such as BMI, waist circumference, WHR, blood glucose and lipids) and expression or concentration of cathelicidin LL-37 35,36 . Interestingly, defensins, which together with cathelicidins belong to the family of AMPs, are also affected by metabolic abnormalities, such as abnormal lipid profile 37 .…”

Section: Discussionmentioning

confidence: 99%

Serum level of cathelicidin LL-37 is increased in euthymic patients with bipolar disorder irrespective of their cardio-metabolic status

Wysokiński

Margulska

Kozłowska

et al. 2019

Arch. Clin. Psychiatry (São Paulo)

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Background: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in patients with bipolar disorder. Objectives: The aim of this study is to re-evaluate serum LL-37 levels in patients with euthymic bipolar disorder and in healthy controls, matched for anthropometric and body composition parameters. Methods: 36 adult patients with euthymic bipolar disorder and 68 nondepressed adults were included into the study. Concentration of LL-37 in serum was assessed using ELISA method. Detailed anthropometric measurements, body composition and biochemical analyses were performed. Results: There was a statistically significant difference (p = 0.01) in serum LL-37 level between patients with bipolar disorder (4.97 ± 7.98 ng/mL) and control subjects (1.78 ± 2.69 ng/mL). Discussion: Results of this study indicate that LL-37 serum level is increased in euthymic bipolar disorder patients. We found that this increase could not be attributed to analyzed anthropometric or body composition parameters.

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Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor

Cited by 37 publications

References 39 publications

Cathelicidin‐related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation

Cathelicidin‐related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation

CD36 Gene Polymorphisms Are Associated with Intracerebral Hemorrhage Susceptibility in a Han Chinese Population

Serum level of cathelicidin LL-37 is increased in euthymic patients with bipolar disorder irrespective of their cardio-metabolic status

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