High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling.

Autor: Chakraborti A; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Graham C; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Chehade S; Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States., Vashi B; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Umfress A; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Kurup P; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Vickers B; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Chen HA; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Telange R; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Berryhill T; Department of Pharmacology, University of Alabama at Birmingham Medical Center, Birmingham, AL, United States., Van Der Pol W; Center for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL, United States., Powell M; Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States., Barnes S; Department of Pharmacology, University of Alabama at Birmingham Medical Center, Birmingham, AL, United States., Morrow C; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United States., Smith DL Jr; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States., Mukhtar MS; Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States., Watts S; Department of Biology, University of Alabama at Birmingham, Birmingham, AL, United States., Kennedy G; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States., Bibb J; Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United States.
Jazyk: angličtina
Zdroj: Frontiers in neuroscience [Front Neurosci] 2021 May 26; Vol. 15, pp. 669410. Date of Electronic Publication: 2021 May 26 (Print Publication: 2021).
DOI: 10.3389/fnins.2021.669410
Abstrakt: The neurobiological mechanisms that mediate psychiatric comorbidities associated with metabolic disorders such as obesity, metabolic syndrome and diabetes remain obscure. High fructose corn syrup (HFCS) is widely used in beverages and is often included in food products with moderate or high fat content that have been linked to many serious health issues including diabetes and obesity. However, the impact of such foods on the brain has not been fully characterized. Here, we evaluated the effects of long-term consumption of a HFCS-Moderate Fat diet (HFCS-MFD) on behavior, neuronal signal transduction, gut microbiota, and serum metabolomic profile in mice to better understand how its consumption and resulting obesity and metabolic alterations relate to behavioral dysfunction. Mice fed HFCS-MFD for 16 weeks displayed enhanced anxiogenesis, increased behavioral despair, and impaired social interactions. Furthermore, the HFCS-MFD induced gut microbiota dysbiosis and lowered serum levels of serotonin and its tryptophan-based precursors. Importantly, the HFCS-MFD altered neuronal signaling in the ventral striatum including reduced inhibitory phosphorylation of glycogen synthase kinase 3β (GSK3β), increased expression of ΔFosB, increased Cdk5-dependent phosphorylation of DARPP-32, and reduced PKA-dependent phosphorylation of the GluR1 subunit of the AMPA receptor. These findings suggest that HFCS-MFD-induced changes in the gut microbiota and neuroactive metabolites may contribute to maladaptive alterations in ventral striatal function that underlie neurobehavioral impairment. While future studies are essential to further evaluate the interplay between these factors in obesity and metabolic syndrome-associated behavioral comorbidities, these data underscore the important role of peripheral-CNS interactions in diet-induced behavioral and brain function. This study also highlights the clinical need to address neurobehavioral comorbidities associated with obesity and metabolic syndrome.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Chakraborti, Graham, Chehade, Vashi, Umfress, Kurup, Vickers, Chen, Telange, Berryhill, Van Der Pol, Powell, Barnes, Morrow, Smith, Mukhtar, Watts, Kennedy and Bibb.)
Databáze: MEDLINE