Universität zu Köln

Kasper, Philipp, Vohlen, Christina, Dinger, Katharina, Mohr, Jasmine, Hucklenbruch-Rother, Eva, Janoschek, Ruth, Koeth, Jessica, Matthes, Jan ORCID: 0000-0003-2754-1555, Appel, Sarah, Doetsch, Joerg and Alcazar, Miguel A. Alejandre (2017). Renal Metabolic Programming Is Linked to the Dynamic Regulation of a Leptin-Klf15 Axis and Akt/AMPK alpha Signaling in Male Offspring of Obese Dams. Endocrinology, 158 (10). S. 3399 - 3416. WASHINGTON: ENDOCRINE SOC. ISSN 1945-7170

Full text not available from this repository.

Abstract

Childhood obesity is associated with renal diseases. Maternal obesity is a risk factor linked to increased adipocytokines and metabolic disorders in the offspring. Therefore, we studied the impact of maternal obesity on renal-intrinsic insulin and adipocytokine signaling and on renal function and structure. To induce maternal obesity, female mice were fed a high-fat diet (HFD) or a standard diet (SD; control group) prior to mating, during gestation, and throughout lactation. A third group of dams was fed HFD only during lactation (HFD-Lac). After weaning at postnatal day (P)21, offspring of all groups received SD. Clinically, HFD offspring were overweight and insulin resistant at P21. Although no metabolic changes were detected at P70, renal sodium excretion was reduced by 40%, and renal matrix deposition increased in the HFD group. Mechanistically, two stages were differentiated. In the early stage (P21), compared with the control group, HFD showed threefold increased white adipose tissue, impaired glucose tolerance, hyperleptinemia, and hyperinsulinemia. Renal leptin/Stat3-signaling was activated. In contrast, the Akt/AMPK alpha cascade and Kruppel-like factor 15 expression were decreased. In the late stage (P70), although no metabolic differences were detected in HFD when compared with the control group, leptin/Stat3-signaling was reduced, and Akt/AMPK alpha was activated in the kidneys. This effect was linked to an increase of proliferative (cyclinD1/D2) and profibrotic (ctgf/collagen III alpha 1) markers, similar to leptin-deficient mice. HFD-Lac mice exhibited metabolic changes at P21 similar to HFD, but no other persistent changes. This study shows a link between maternal obesity and metabolic programming of renal structure and function and intrinsic-renal Stat3/Akt/AMPK alpha signaling in the offspring.This study proposes a two-stage animal disease model for early origins of renal dysfunction and identifies molecular mechanisms of renal metabolic programming after maternal obesity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kasper, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohr, Jasmine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeth, Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthes, Jan UNSPECIFIED orcid.org/0000-0003-2754-1555 UNSPECIFIED Appel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-215341
DOI:	10.1210/en.2017-00489
Journal or Publication Title:	Endocrinology
Volume:	158
Number:	10
Page Range:	S. 3399 - 3416
Date:	2017
Publisher:	ENDOCRINE SOC
Place of Publication:	WASHINGTON
ISSN:	1945-7170
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED PROTEIN-KINASE; HIGH-FAT DIET; CHRONIC KIDNEY-DISEASE; NF-KAPPA-B; CHILDHOOD OBESITY; BARIATRIC SURGERY; AMPK; INSULIN; INFLAMMATION; WEIGHT Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21534