Exp Clin Endocrinol Diabetes 2020; 128(01): 20-29
DOI: 10.1055/a-0735-9533
Article
© Georg Thieme Verlag KG Stuttgart · New York

Impact of Brain Fatty Acid Signaling on Peripheral Insulin Action in Mice

Susanne Neschen
1  Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
2  German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Moya Wu
1  Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
2  German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Christiane Fuchs
3  Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
4  Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technical University of Munich, Garching, Germany
,
Ivan Kondofersky
3  Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
4  Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technical University of Munich, Garching, Germany
,
Fabian J. Theis
3  Institute of Computational Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
4  Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technical University of Munich, Garching, Germany
,
Martin Hrabě de Angelis
1  Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
2  German Center for Diabetes Research (DZD), Neuherberg, Germany
,
Hans-Ulrich Häring
2  German Center for Diabetes Research (DZD), Neuherberg, Germany
5  Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany
6  Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen (IDM), Tuebingen, Germany
,
Tina Sartorius
2  German Center for Diabetes Research (DZD), Neuherberg, Germany
5  Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University of Tuebingen, Tuebingen, Germany
6  Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen (IDM), Tuebingen, Germany
› Author Affiliations
Funding: This study was supported by a grant from German Center for Diabetes Research (DZD e.V.) to TS and SN. We further acknowledge support by the German Federal Ministry of Education and Research (BMBF; DLR01GI0925) to the German Center for Diabetes Research (DZD e.V.). CF, IK and FJT received funding from the European Research Council under grant agreement n° 259294 (Starting grant Latent Causes) and the German Research Foundation (DFG) within the Collaborative Research Centre 1243, Subproject A17. We further acknowledge support by Open Access Publishing Fund of University of Tuebingen.
Further Information

Publication History

received 02 July 2018
revised 01 August 2018

accepted 10 September 2018

Publication Date:
05 November 2018 (online)

Abstract

Aims and Methods Glucose homeostasis and energy balance are under control by peripheral and brain processes. Especially insulin signaling in the brain seems to impact whole body glucose homeostasis and interacts with fatty acid signaling. In humans circulating saturated fatty acids are negatively associated with brain insulin action while animal studies suggest both positive and negative interactions of fatty acids and insulin brain action. This apparent discrepancy might reflect a difference between acute and chronic fatty acid signaling. To address this question we investigated the acute effect of an intracerebroventricular palmitic acid administration on peripheral glucose homeostasis. We developed and implemented a method for simultaneous monitoring of brain activity and peripheral insulin action in freely moving mice by combining radiotelemetry electrocorticography (ECoG) and euglycemic-hyperinsulinemic clamps. This method allowed gaining insight in the early kinetics of brain fatty acid signaling and its contemporaneous effect on liver function in vivo, which, to our knowledge, has not been assessed so far in mice.

Results Insulin-induced brain activity in the theta and beta band was decreased by acute intracerebroventricular application of palmitic acid. Peripherally it amplified insulin action as demonstrated by a significant inhibition of endogenous glucose production and increased glucose infusion rate. Moreover, our results further revealed that the brain effect of peripheral insulin is modulated by palmitic acid load in the brain.

Conclusion These findings suggest that insulin action is amplified in the periphery and attenuated in the brain by acute palmitic acid application. Thus, our results indicate that acute palmitic acid signaling in the brain may be different from chronic effects.

Supporting Information