mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and
protects against gestational diabetes in mice and humans.
Authors Rojas-Rodriguez R, Ziegler R, DeSouza T, Majid S, Madore AS, Amir N, Pace VA,
Nachreiner D, Alfego D, Mathew J, Leung K, Moore Simas TA, Corvera S
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Science translational medicine
Year 2020
Date Published 11/1/2020
Volume : Pages 12 : Not Specified
PubMed Reference 33239385
Abstract Pregnancy is a physiological state of continuous adaptation to changing maternal
and fetal nutritional needs, including a reduction of maternal insulin
sensitivity allowing for appropriately enhanced glucose availability to the
fetus. However, excessive insulin resistance in conjunction with insufficient
insulin secretion results in gestational diabetes mellitus (GDM), greatly
increasing the risk for pregnancy complications and predisposing both mothers
and offspring to future metabolic disease. Here, we report a signaling pathway
connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue
expansion in pregnancy. Adipose tissue plays a central role in the regulation of
insulin sensitivity, and we show that, in both mice and humans, pregnancy caused
remodeling of adipose tissue evidenced by altered adipocyte size,
vascularization, and in vitro expansion capacity. PAPPA is known to be a
metalloprotease secreted by human placenta that modulates insulin-like growth
factor (IGF) bioavailability through prolteolysis of IGF binding proteins
(IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex
vivo human adipose tissue expansion in an IGFBP-5- and IGF-1-dependent manner.
Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling,
pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating
multiple aspects of human GDM. In a cohort of 6361 pregnant women,
concentrations of circulating PAPPA are inversely correlated with glycemia and
odds of developing GDM. These data identify PAPPA and the IGF signaling pathway
as necessary for the regulation of maternal adipose tissue physiology and
systemic glucose homeostasis, with consequences for long-term metabolic risk and
potential for therapeutic use.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.