Journal Article

DKFZ-2017-05112

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution.

Maida, A. ; Zota, A. ; Sjøberg, K. A. ; Schumacher, J.DKFZ* ; Sijmonsma, T.DKFZ* ; Pfenninger, A. ; Christensen, M. M. ; Gantert, T.DKFZ* ; Fuhrmeister, J.DKFZ* ; Rothermel, U.DKFZ* ; Schmoll, D. ; Heikenwälder, M.DKFZ* ; Iovanna, J. L. ; Stemmer, K. ; Kiens, B. ; Herzig, S.Extern* ; Rose, A. J. (Last author)DKFZ*

2016
ASCJ Ann Arbor, Mich.

This record in other databases:  

Please use a persistent id in citations: doi:10.1172/JCI85946

Abstract: Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake. DPD-mediated metabolic inefficiency and improvement of glucose homeostasis were independent of uncoupling protein 1 (UCP1), but required expression of liver-derived fibroblast growth factor 21 (FGF21) in both lean and obese mice. FGF21 expression and secretion as well as the associated metabolic remodeling induced by DPD also required induction of liver-integrated stress response-driven nuclear protein 1 (NUPR1). Insufficiency of select nonessential amino acids (NEAAs) was necessary and adequate for NUPR1 and subsequent FGF21 induction and secretion in hepatocytes in vitro and in vivo. Taken together, these data indicate that DPD promotes improved glucose homeostasis through an NEAA insufficiency-induced liver NUPR1/FGF21 axis.

Keyword(s): Basic Helix-Loop-Helix Transcription Factors ; DNA-Binding Proteins ; Dietary Proteins ; Neoplasm Proteins ; Nupr1 protein, mouse ; P8 protein, human ; UCP1 protein, human ; Ucp1 protein, mouse ; Uncoupling Protein 1 ; fibroblast growth factor 21 ; Fibroblast Growth Factors ; Glucose

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Contributing Institute(s):

1. Chronische Entzündung und Krebs (F180)
2. Zelluläre und Molekulare Pathologie (G130)
3. Molekulare Stoffwechselkontrolle (A170)
4. Metabolismus und Stammzellplastizität (A171)

Research Program(s):

1. 323 - Metabolic Dysfunction as Risk Factor (POF3-323) (POF3-323)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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