The adipokine C1q/TNF-related protein-3 (CTRP-3) inhibits Toll-like receptor (TLR)-induced expression of Cathelicidin antimicrobial peptide (CAMP) in adipocytes

Karrasch, Thomas; Höpfinger, Alexandra; Schäffler, Andréas; Schmid, Andreas

doi:10.1016/j.cyto.2021.155663

Cited by 7 publications

(4 citation statements)

References 55 publications

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“…However, the relationship of CTRP3 with DPN is not fully understand. CTRP3 was previously revealed to be an anti-inflammatory adipokine that inhibits proinflammatory pathways mediated by LPS-like and Toll-like receptor in monocytes and adipocyte 34. Recent study also found that CTRP3 may exert vasculoprotective effects via the adiponectin receptor 1/AMPK/eNOS-dependent/NO pathway 35.…”

Section: Discussionmentioning

confidence: 93%

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy

Lin

Liu

Xiong

et al. 2022

BMJ Open Diab Res Care

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IntroductionTo analyze the associations of circulating C1q/tumor necrosis factor-related protein-3 (CTRP3) concentrations with several metabolic parameters and to investigate the possible role of CTRP3 in subjects with diabetic peripheral neuropathy (DPN).Research design and methodsA total of 347 participants were recruited in this study, and plasma CTRP3 concentrations were analyzed in subjects with DPN (n=172) and without DPN (non-DPN, n=175). The nerve conduction test and oral glucose tolerance test were performed, and Neuropathy Symptom Score (NSS)/Neuropathy Disability Score (NDS) and biochemical parameters were measured in all participants.ResultsPlasma CTRP3 concentrations were significantly lower in patients with DPN compared with those in patients with diabetes without DPN (p<0.01), despite the comparable glucose and lipid metabolism levels in both groups. Groups with a higher plasma CTRP3 level had a faster nerve conduction velocity. In addition, plasma CTRP3 concentrations were negatively correlated with hemoglobin A1c (HbA1c), urea acid (UA), triglyceride, NSS and NDS (p<0.05) after being adjusted for age and sex. Multivariate logistic regression analysis revealed that plasma CTRP3 concentrations were significantly correlated with DPN after being controlled for age, sex, body mass index, HbA1c, blood pressure, lipid profiles, and renal function.ConclusionsPlasma CTRP3 concentrations were significantly lower in patients with DPM and positively correlated with nerve conduction velocity. The relationship between CTRP3 levels and DPN is independent of the glucose and lipid status. Therefore, circulating CTRP3 might serve as a predictor of impairment of nerve conduction in patients with DPN.

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Section: Discussionmentioning

confidence: 93%

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy

Lin

Liu

Xiong

et al. 2022

BMJ Open Diab Res Care

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“…Activation of TLR2 and TLR4 by specific ligands (MALP2, lipopolysaccharides (LPS)) up-regulates adipocyte CAMP expression involving classical signal transduction elements such as NF-κB, PI3K and STAT3 [16]. This TLR-mediated proinflammatory activation of CAMP expression can be modified by immunomodulatory adipokines such as C1q/TNF-related protein-3 (CTRP-3) [17]. Furthermore, immuno-metabolic factors, such as bile acids, glucose, insulin, and incretins, are able to modulate CAMP expression in adipocytes in vitro [15].…”

Section: Of 16mentioning

confidence: 99%

Regulation of Cathelicidin Antimicrobial Peptide (CAMP) Gene Expression by TNFα and cfDNA in Adipocytes

Höpfinger,

Schmid,

Schweitzer

et al. 2023

IJMS

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Understanding the complex interactions between metabolism and the immune system (“metaflammation”) is crucial for the identification of key immunomodulatory factors as potential therapeutic targets in obesity and in cardiovascular diseases. Cathelicidin antimicrobial peptide (CAMP) is an important factor of innate immunity and is expressed in adipocytes. CAMP, therefore, might play a role as an adipokine in metaflammation and adipose inflammation. TNFα, cell-free nucleic acids (cfDNA), and toll-like receptor (TLR) 9 are components of the innate immune system and are functionally active in adipose tissue. The aim of the present study was to investigate the impact of TNFα and cfDNA on CAMP expression in adipocytes. Since cfDNA acts as a physiological TLR9 agonist, we additionally investigated TLR9-mediated CAMP regulation in adipocytes and adipose tissue. CAMP gene expression in murine 3T3-L1 and human SGBS adipocytes and in murine and human adipose tissues was quantified by real-time PCR. Adipocyte inflammation was induced in vitro by TNFα and cfDNA stimulation. Serum CAMP concentrations in TLR9 knockout (KO) and in wildtype mice were quantified by ELISA. In primary adipocytes of wildtype and TLR9 KO mice, CAMP gene expression was quantified by real-time PCR. CAMP gene expression was considerably increased in 3T3-L1 and SGBS adipocytes during differentiation. TNFα significantly induced CAMP gene expression in mature adipocytes, which was effectively antagonized by inhibition of PI3K signaling. Cell-free nucleic acids (cfDNA) significantly impaired CAMP gene expression, whereas synthetic agonistic and antagonistic TLR9 ligands had no effect. CAMP and TLR9 gene expression were correlated positively in murine and human subcutaneous but not in intra-abdominal/visceral adipose tissues. Male TLR9 knockout mice exhibited lower systemic CAMP concentrations than wildtype mice. CAMP gene expression levels in primary adipocytes did not significantly differ between wildtype and TLR9 KO mice. These findings suggest a regulatory role of inflammatory mediators, such as TNFα and cfDNA, in adipocytic CAMP expression as a novel putative molecular mechanism in adipose tissue innate immunity.

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“…Among these very heterogenous factors, adipose-derived Cathelicidin antimicrobial peptide (CAMP; also: LL37, CAP-18) has gained particular attention due to its crucial role in host defense against subdermal infection [ 9 ]. Previous investigation has further elucidated its regulation in adipose tissue and adipocyte innate immunity [ 10 , 11 ]. Of note, a recent study on a cohort of morbidly obese individuals undergoing weight loss therapy revealed circulating CAMP to be induced upon bariatric surgery, potentially involving effects mediated by systemic bile acids and incretins [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Concentrations of Cathelicidin Anti-Microbial Peptide (CAMP) Are Increased during Oral Glucose Tolerance Test

Höpfinger,

Karrasch,

Schäffler

et al. 2023

IJMS

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Recent investigation has revealed the significant role of Cathelicidin antimicrobial peptide (CAMP) in infection defense and innate immunity processes in adipose tissue. Meanwhile, knowledge of its regulation and functions in metabolic contexts as an adipokine remains sparce. The present study investigated the postprandial regulation of circulating CAMP levels during oral glucose tolerance tests (OGTTs). Eighty-six metabolically healthy volunteers participated in a standardized 75 g-2 h-OGTT setting. The effects of exogenous glucose, insulin, and incretins on CAMP expression in human adipocyte culture (cell-line SGBS) were studied in vitro. CAMP concentrations in blood serum samples were measured by ELISA techniques and adipocyte gene expression levels were quantified by real-time PCR. Of note, base-line CAMP serum quantities were negatively correlated with HDL cholesterol levels as well as with the anti-inflammatory adipokine adiponectin. During the 2 h following glucose ingestion, a significant rise in circulating CAMP concentrations was observed in considerable contrast to reduced quantities of fatty acid binding proteins (FABP) 2 and 4 and dipeptidyl peptidase 4 (DPP4). In SGBS adipocytes, neither differing glucose levels nor insulin or incretin treatment significantly induced CAMP mRNA levels. According to our data, glucose represents a positive postprandial regulator of systemic CAMP. This effect apparently is not mediated by the regulatory impact of glucose metabolism on adipocyte CAMP expression.

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The adipokine C1q/TNF-related protein-3 (CTRP-3) inhibits Toll-like receptor (TLR)-induced expression of Cathelicidin antimicrobial peptide (CAMP) in adipocytes

Cited by 7 publications

References 55 publications

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy

Plasma C1q/tumor necrosis factor-related protein-3 concentrations are associated with diabetic peripheral neuropathy

Regulation of Cathelicidin Antimicrobial Peptide (CAMP) Gene Expression by TNFα and cfDNA in Adipocytes

Circulating Concentrations of Cathelicidin Anti-Microbial Peptide (CAMP) Are Increased during Oral Glucose Tolerance Test

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