High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling
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 cont...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.669410/full |
| _version_ | 1818832519471038464 |
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| author | Ayanabha Chakraborti Christopher Graham Sophie Chehade Bijal Vashi Alan Umfress Pradeep Kurup Benjamin Vickers H. Alexander Chen Rahul Telange Taylor Berryhill William Van Der Pol Mickie Powell Stephen Barnes Casey Morrow Daniel L. Smith M. Shahid Mukhtar Stephen Watts Gregory Kennedy James Bibb |
| author_facet | Ayanabha Chakraborti Christopher Graham Sophie Chehade Bijal Vashi Alan Umfress Pradeep Kurup Benjamin Vickers H. Alexander Chen Rahul Telange Taylor Berryhill William Van Der Pol Mickie Powell Stephen Barnes Casey Morrow Daniel L. Smith M. Shahid Mukhtar Stephen Watts Gregory Kennedy James Bibb |
| author_sort | Ayanabha Chakraborti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T02:04:19Z |
| format | Article |
| id | doaj.art-311736e5173640d0ae0f6fbcd37c08c7 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-19T02:04:19Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-311736e5173640d0ae0f6fbcd37c08c72022-12-21T20:40:59ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-05-011510.3389/fnins.2021.669410669410High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal SignalingAyanabha Chakraborti0Christopher Graham1Sophie Chehade2Bijal Vashi3Alan Umfress4Pradeep Kurup5Benjamin Vickers6H. Alexander Chen7Rahul Telange8Taylor Berryhill9William Van Der Pol10Mickie Powell11Stephen Barnes12Casey Morrow13Daniel L. Smith14M. Shahid Mukhtar15Stephen Watts16Gregory Kennedy17James Bibb18Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Pharmacology, University of Alabama at Birmingham Medical Center, Birmingham, AL, United StatesCenter for Clinical and Translational Science, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Pharmacology, University of Alabama at Birmingham Medical Center, Birmingham, AL, United StatesDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fnins.2021.669410/fulldiethigh fructose corn syrup (HFCS)anxietydepressionnucleus accumbenstryptophan |
| spellingShingle | Ayanabha Chakraborti Christopher Graham Sophie Chehade Bijal Vashi Alan Umfress Pradeep Kurup Benjamin Vickers H. Alexander Chen Rahul Telange Taylor Berryhill William Van Der Pol Mickie Powell Stephen Barnes Casey Morrow Daniel L. Smith M. Shahid Mukhtar Stephen Watts Gregory Kennedy James Bibb High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling Frontiers in Neuroscience diet high fructose corn syrup (HFCS) anxiety depression nucleus accumbens tryptophan |
| title | High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling |
| title_full | High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling |
| title_fullStr | High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling |
| title_full_unstemmed | High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling |
| title_short | High Fructose Corn Syrup-Moderate Fat Diet Potentiates Anxio-Depressive Behavior and Alters Ventral Striatal Neuronal Signaling |
| title_sort | high fructose corn syrup moderate fat diet potentiates anxio depressive behavior and alters ventral striatal neuronal signaling |
| topic | diet high fructose corn syrup (HFCS) anxiety depression nucleus accumbens tryptophan |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.669410/full |
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