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Cell Mol Life Sci. 2018 Feb;75(4):727-742. doi: 10.1007/s00018-017-2658-y. Epub 2017 Sep 20.

Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo.

Author information

1
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Brüderstr. 34, 04103, Leipzig, Germany.
2
Department of Medicine, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.
3
German Center for Diabetes Research (DZD), Munich, Germany.
4
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
5
IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
6
Department of Medicine, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany. matthias.blueher@medizin.uni-leipzig.de.
7
IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany. matthias.blueher@medizin.uni-leipzig.de.
8
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Brüderstr. 34, 04103, Leipzig, Germany. jheiker@uni-leipzig.de.
9
Department of Medicine, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany. jheiker@uni-leipzig.de.
10
IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany. jheiker@uni-leipzig.de.

Abstract

Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function. Therefore, we have inactivated the Klk7 gene in adipose tissue using conditional gene-targeting strategies in mice. Klk7-deficient mice (ATKlk7 -/-) exhibited less weight gain, predominant expansion of subcutaneous adipose tissue and improved whole body insulin sensitivity under a high fat diet (HFD). ATKlk7 -/- mice displayed higher energy expenditure and food intake, most likely due to altered adipokine secretion including lower circulating leptin. Pro-inflammatory cytokine expression was significantly reduced in combination with an increased percentage of alternatively activated (anti-inflammatory) M2 macrophages in epigonadal adipose tissue of ATKlk7 -/-. Taken together, by attenuating adipose tissue inflammation, altering adipokine secretion and epigonadal adipose tissue expansion, Klk7 deficiency in adipose tissue partially ameliorates the adverse effects of HFD-induced obesity. In summary, we provide first evidence for a previously unrecognized role of KLK7 in adipose tissue with effects on whole body energy expenditure and insulin sensitivity.

KEYWORDS:

Adiposity; Insulin resistance; Metabolic syndrome; Serine proteases; Serpin

PMID:
28932870
PMCID:
PMC5769829
DOI:
10.1007/s00018-017-2658-y
[Indexed for MEDLINE]
Free PMC Article

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