Abstract

Secreted FGF binding proteins (FGFBP) mobilize locally-acting paracrine FGFs from their extracellular storage. Here, we report that FGFBP3 (BP3) modulates fat and glucose metabolism in mouse models of metabolic syndrome. BP3 knockout mice exhibited altered lipid metabolism pathways with reduced hepatic and serum triglycerides. In obese mice the expression of exogenous BP3 reduced hyperglycemia, hepatosteatosis and weight gain, blunted de novo lipogenesis in liver and adipose tissues, increased circulating adiponectin and decreased NEFA. The BP3 protein interacts with endocrine FGFs through its C-terminus and thus enhances their signaling. We propose that BP3 may constitute a new therapeutic to reverse the pathology associated with metabolic syndrome that includes nonalcoholic fatty liver disease and type 2 diabetes mellitus.

Details

Title
Fibroblast Growth Factor Binding Protein 3 (FGFBP3) impacts carbohydrate and lipid metabolism
Author
Tassi, Elena 1 ; Garman, Khalid A 1 ; Schmidt, Marcel O 1 ; Ma, Xiaoting 1 ; Kabbara, Khaled W 1 ; Uren, Aykut 1 ; Tomita, York 1 ; Goetz, Regina 2 ; Mohammadi, Moosa 2 ; Wilcox, Christopher S 3 ; Riegel, Anna T 1 ; Carlstrom, Mattias 4 ; Wellstein, Anton 1   VIAFID ORCID Logo 

1  Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, School of Medicine, Washington, DC, USA 
2  Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA 
3  Division of Nephrology and Hypertension, Kidney, and Vascular Research Center, Georgetown University, School of Medicine, Washington, DC, USA 
4  Division of Nephrology and Hypertension, Kidney, and Vascular Research Center, Georgetown University, School of Medicine, Washington, DC, USA; Department of Physiology & Pharmacology, Karolinska Institutet S-17177, Stockholm, Sweden 
Pages
1-14
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-34238-5
ProQuest document ID
2126881826
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.