Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice

Research output: Contribution to journalJournal articleResearchpeer-review

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Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice. / Larsen, Ida Søgaard; Fritzen, Andreas Mæchel; Carl, Christian Strini; Agerholm, Marianne; Damgaard, Mads Thue Fejerskov; Holm, Jacob Bak; Marette, Andre; Nordkild, Peter; Kiens, Bente; Kristiansen, Karsten; Wehkamp, Jan; Jensen, Benjamin Anderschou Holbech.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 317, No. 1, 2019, p. E42-E52.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Larsen, IS, Fritzen, AM, Carl, CS, Agerholm, M, Damgaard, MTF, Holm, JB, Marette, A, Nordkild, P, Kiens, B, Kristiansen, K, Wehkamp, J & Jensen, BAH 2019, 'Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice', American Journal of Physiology: Endocrinology and Metabolism, vol. 317, no. 1, pp. E42-E52. https://doi.org/10.1152/ajpendo.00019.2019

APA

Larsen, I. S., Fritzen, A. M., Carl, C. S., Agerholm, M., Damgaard, M. T. F., Holm, J. B., ... Jensen, B. A. H. (2019). Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice. American Journal of Physiology: Endocrinology and Metabolism, 317(1), E42-E52. https://doi.org/10.1152/ajpendo.00019.2019

Vancouver

Larsen IS, Fritzen AM, Carl CS, Agerholm M, Damgaard MTF, Holm JB et al. Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice. American Journal of Physiology: Endocrinology and Metabolism. 2019;317(1):E42-E52. https://doi.org/10.1152/ajpendo.00019.2019

Author

Larsen, Ida Søgaard ; Fritzen, Andreas Mæchel ; Carl, Christian Strini ; Agerholm, Marianne ; Damgaard, Mads Thue Fejerskov ; Holm, Jacob Bak ; Marette, Andre ; Nordkild, Peter ; Kiens, Bente ; Kristiansen, Karsten ; Wehkamp, Jan ; Jensen, Benjamin Anderschou Holbech. / Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice. In: American Journal of Physiology: Endocrinology and Metabolism. 2019 ; Vol. 317, No. 1. pp. E42-E52.

Bibtex

@article{dbdbd38e28d148b8bb5dfd1938ea5322,
title = "Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice",
abstract = "Objective: Overnutrition is the principal cause of insulin resistance (IR) and dyslipidemia, which drive non-alcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations and change-of-function in gut-lining cell populations including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human alpha-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity.Methods: Mice were fed a 60{\%}HFD for 13 weeks and subsequently treated with physiologically relevant amounts of HD-5 (0,001{\%}) or vehicle for 10 weeks. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. Fresh fecal samples were collected immediately before and after intervention. Small intestine samples were harvested at necropsy. Plasma and liver lipid and protein profiles were determined by biochemical analyses.Results: HD-5 treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma- and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, whichcorrelated inversely with metabolic dysfunctions.Conclusion: This study provides proof-of-concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR and NAFLD.",
keywords = "Faculty of Science, Human defensins, Diet induced obesity, Insulin resistance, NAFLD, Host-microbe interactions",
author = "Larsen, {Ida S{\o}gaard} and Fritzen, {Andreas M{\ae}chel} and Carl, {Christian Strini} and Marianne Agerholm and Damgaard, {Mads Thue Fejerskov} and Holm, {Jacob Bak} and Andre Marette and Peter Nordkild and Bente Kiens and Karsten Kristiansen and Jan Wehkamp and Jensen, {Benjamin Anderschou Holbech}",
note = "CURIS 2019 NEXS 221",
year = "2019",
doi = "10.1152/ajpendo.00019.2019",
language = "English",
volume = "317",
pages = "E42--E52",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "1",

}

RIS

TY - JOUR

T1 - Human Paneth cell α-defensin-5 treatment reverses dyslipidemia and improves glucoregulatory capacity in diet-induced obese mice

AU - Larsen, Ida Søgaard

AU - Fritzen, Andreas Mæchel

AU - Carl, Christian Strini

AU - Agerholm, Marianne

AU - Damgaard, Mads Thue Fejerskov

AU - Holm, Jacob Bak

AU - Marette, Andre

AU - Nordkild, Peter

AU - Kiens, Bente

AU - Kristiansen, Karsten

AU - Wehkamp, Jan

AU - Jensen, Benjamin Anderschou Holbech

N1 - CURIS 2019 NEXS 221

PY - 2019

Y1 - 2019

N2 - Objective: Overnutrition is the principal cause of insulin resistance (IR) and dyslipidemia, which drive non-alcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations and change-of-function in gut-lining cell populations including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human alpha-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity.Methods: Mice were fed a 60%HFD for 13 weeks and subsequently treated with physiologically relevant amounts of HD-5 (0,001%) or vehicle for 10 weeks. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. Fresh fecal samples were collected immediately before and after intervention. Small intestine samples were harvested at necropsy. Plasma and liver lipid and protein profiles were determined by biochemical analyses.Results: HD-5 treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma- and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, whichcorrelated inversely with metabolic dysfunctions.Conclusion: This study provides proof-of-concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR and NAFLD.

AB - Objective: Overnutrition is the principal cause of insulin resistance (IR) and dyslipidemia, which drive non-alcoholic fatty liver disease (NAFLD). Overnutrition is further linked to disrupted bowel function, microbiota alterations and change-of-function in gut-lining cell populations including Paneth cells of the small intestine. Paneth cells regulate microbial diversity through expression of antimicrobial peptides, particularly human alpha-defensin-5 (HD-5), and have shown repressed secretory capacity in human obesity.Methods: Mice were fed a 60%HFD for 13 weeks and subsequently treated with physiologically relevant amounts of HD-5 (0,001%) or vehicle for 10 weeks. The glucoregulatory capacity was determined by glucose tolerance tests and measurements of corresponding insulin concentrations both before and during intervention. Gut microbiome composition was examined by 16S rRNA gene amplicon sequencing. Fresh fecal samples were collected immediately before and after intervention. Small intestine samples were harvested at necropsy. Plasma and liver lipid and protein profiles were determined by biochemical analyses.Results: HD-5 treated mice exhibited improved glucoregulatory capacity along with an ameliorated plasma- and liver lipid profile. This was accompanied by specific decrease in jejunal inflammation and gut microbiota alterations including increased Bifidobacterium abundances, whichcorrelated inversely with metabolic dysfunctions.Conclusion: This study provides proof-of-concept for the use of human defensins to improve host metabolism by mitigating the triad cluster of dyslipidemia, IR and NAFLD.

KW - Faculty of Science

KW - Human defensins

KW - Diet induced obesity

KW - Insulin resistance

KW - NAFLD

KW - Host-microbe interactions

U2 - 10.1152/ajpendo.00019.2019

DO - 10.1152/ajpendo.00019.2019

M3 - Journal article

C2 - 30860877

VL - 317

SP - E42-E52

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -

ID: 214870271