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Sartorius, T. ; Drescher, A.* ; Panse, M.* ; Lastovicka, P.* ; Peter, A.* ; Weigert, C. ; Kostenis, E.* ; Ullrich, S.* ; Häring, H.-U.

Mice lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are protected against conjugated linoleic acid-induced fatty liver but develop inflammation and insulin resistance in the brain.

Cell. Physiol. Biochem. 35, 2272-2284 (2015)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND/AIMS: Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. METHODS AND RESULTS: After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1(-/-)) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1(-/-) mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1(-/-) mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. CONCLUSION: This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cla ; Electrocorticography ; Ffar1(-/-) Mouse ; Ffar1 ; Gpr40 ; Insulin Resistance ; Fatty Liver ; Brain Insulin Resistance ; Brain Inflammation ; Radiotelemetry; Central-nervous-system; Trans-10,cis-12 Isomer; Adipose-tissue; Gpr40; Neurons; Cells; Supplementation; Neurogenesis; Stimulation; Expression
ISSN (print) / ISBN 1015-8987
e-ISSN 1421-9778
Quellenangaben Band: 35, Heft: 6, Seiten: 2272-2284 Artikelnummer: , Supplement: ,
Verlag Karger
Verlagsort Basel
Begutachtungsstatus Peer reviewed