CC BY-NC-ND 4.0 · Horm Metab Res 2021; 53(03): 169-177
DOI: 10.1055/a-1323-3050
Endocrine Care

Serum Levels and Adipose Tissue Gene Expression of Cathelicidin Antimicrobial Peptide (CAMP) in Obesity and During Weight Loss

Alexandra Hochberg
1   Department of Internal Medicine III, University of Giessen, Giessen, Germany
,
Marissa Patz
1   Department of Internal Medicine III, University of Giessen, Giessen, Germany
,
Thomas Karrasch
1   Department of Internal Medicine III, University of Giessen, Giessen, Germany
,
Andreas Schäffler
1   Department of Internal Medicine III, University of Giessen, Giessen, Germany
,
Andreas Schmid
1   Department of Internal Medicine III, University of Giessen, Giessen, Germany
› Institutsangaben

Abstract

CAMP (Cathelicidin antimicrobial peptide) is synthesized and secreted by adipocytes and involved in adipose tissue (AT) innate immune response and host defense of subcutaneous AT against Gram positive bacteria. Data on the regulation of CAMP in obesity and during weight loss are scarce and reference values do not exist. Serum CAMP levels (ELISA) and AT gene expression levels (quantitative real time PCR) were investigated in two large and longitudinal (12 months) cohorts of severely obese patients undergoing either a low calorie diet (LCD; n=79) or bariatric surgery (BS; n=156). The impact of metabolic factors on CAMP expression in vitro was investigated in differentiated 3T3-L1 adipocytes. CAMP serum levels significantly increased after BS but not during LCD. Females had lower CAMP serum levels and lower gene expression levels in subcutaneous AT. CAMP was positively correlated to unfavorable metabolic factors/adipokines and negatively to favorable factors/adipokines. CAMP gene expression was higher in subcutaneous than in visceral AT but serum CAMP levels were not correlated to levels of AT gene expression. While certain bile acids upregulated CAMP expression in vitro, high glucose/insulin as well as GLP-1 had an inhibitory effect. There exist gender-specific and AT compartment-specific effects on the regulation of CAMP gene expression. Weight loss induced by BS (but not by LCD) upregulated CAMP serum levels suggesting the involvement of weight loss-independent mechanisms in CAMP regulation such as bile acids, incretins and metabolic factors. CAMP might represent an adipokine at the interface between metabolism and innate immune response.



Publikationsverlauf

Eingereicht: 21. August 2020

Angenommen nach Revision: 17. November 2020

Artikel online veröffentlicht:
12. Januar 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Lee EY, Lee MW, Wong GCL. Modulation of toll-like receptor signaling by antimicrobial peptides. Semin Cell Dev Biol 2019; 88: 178-184
  • 2 Sorensen OE, Follin P, Johnsen AH. et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 2001; 97: 3951-3959
  • 3 Koczulla R, von Degenfeld G, Kupatt C. et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 2003; 111: 1665-1672
  • 4 Zhang LJ, Guerrero-Juarez CF, Hata T. et al. Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 2015; 347: 67-71
  • 5 Alcorn JF, Kolls JK. Physiology. Killer fat. Science 2015; 347: 26-27
  • 6 Schmid A, Karrasch T, Thomalla M. et al. Innate immunity of adipose tissue in rodent models of local and systemic staphylococcus aureus infection. Mediators Inflamm 2017; 2017: 5315602
  • 7 Liggins MC, Li F, Zhang LJ. et al. Retinoids Enhance the expression of cathelicidin antimicrobial peptide during reactive dermal adipogenesis. J Immunol 2019; 203: 1589-1597
  • 8 Brock J, Schmid A, Karrasch T. et al. Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery. Clin Endocrinol (Oxf) 2019; 91: 400-410
  • 9 Green H, Kehinde O. An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 1975; 5: 19-27
  • 10 Zaitsu H, Serrero G. Pedersen fetuin contains three adipogenic factors with distinct biochemical characteristics. J Cell Physiol 1990; 144: 485-491
  • 11 Bachmeier M, Loffler G. Adipogenic activities in commercial preparations of fetuin. Horm Metab Res 1994; 26: 92-96
  • 12 Green H, Kehinde O. Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J Cell Physiol 1979; 101: 169-171
  • 13 Green H, Meuth M. An established pre-adipose cell line and its differentiation in culture. Cell 1974; 3: 127-133
  • 14 Cornelius P, MacDougald OA, Lane MD. Regulation of adipocyte development. Annu Rev Nutr 1994; 14: 99-129
  • 15 MacDougald OA, Lane MD. Transcriptional regulation of gene expression during adipocyte differentiation. Annu Rev Biochem 1995; 64: 345-373
  • 16 Singh P, Zhang Y, Sharma P. et al. Statins decrease leptin expression in human white adipocytes. Physiol Rep 2018; 6: 13566
  • 17 Penney NC, Kinross J, Newton RC. et al. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes 2015; 39: 1565-1574
  • 18 Noel OF, Still CD, Argyropoulos G. et al. Bile acids, fxr, and metabolic effects of bariatric surgery. J Obes 2016; 2016: 4390254
  • 19 Ionut V, Burch M, Youdim A. et al. Gastrointestinal hormones and bariatric surgery-induced weight loss. Obesity 2013; 21: 1093-1103
  • 20 Argyropoulos G. Bariatric surgery: prevalence, predictors, and mechanisms of diabetes remission. Curr Diabetes Rep 2015; 15: 15
  • 21 Schmid A, Hochberg A, Kreiss AF. et al. Role of progranulin in adipose tissue innate immunity. Cytokine 2020; 125: 154796
  • 22 Schaffler A, Muller-Ladner U, Scholmerich J. et al. Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev 2006; 27: 449-467
  • 23 Bargut TCL, Souza-Mello V, Aguila MB. et al. Browning of white adipose tissue: lessons from experimental models. Horm Mol Biol Clinical Invest 2017; 31:hmbci.2017.31.issue-1/hmbci-2016-0051/hmbci-2016-0051.xml. DOI: 10.1515/hmbci-2016-0051.
  • 24 Schmid A, Schlegel J, Thomalla M. et al. Evidence of functional bile acid signaling pathways in adipocytes. Mol Cell Endocrinol 2019; 483: 1-10
  • 25 Schmid A, Neumann H, Karrasch T. et al. Bile acid metabolome after an oral lipid tolerance test by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). PLoS One 2016; 11: e0148869
  • 26 Wang TT, Nestel FP, Bourdeau V. et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173: 2909-2912