Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice
Western diets high in sugars and saturated fats have been reported to induce metabolic and inflammatory impairments that are associated with several age-related disorders, including Alzheimer’s disease (AD) and type 2 diabetes (T2D). The apolipoprotein E (<i>APOE</i>) genotype is associa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/2/287 |
| _version_ | 1797619344554852352 |
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| author | Amy Christensen Christian J. Pike |
| author_facet | Amy Christensen Christian J. Pike |
| author_sort | Amy Christensen |
| collection | DOAJ |
| description | Western diets high in sugars and saturated fats have been reported to induce metabolic and inflammatory impairments that are associated with several age-related disorders, including Alzheimer’s disease (AD) and type 2 diabetes (T2D). The apolipoprotein E (<i>APOE</i>) genotype is associated with metabolic and inflammatory outcomes that contribute to risks for AD and T2D, with the <i>APOE4</i> genotype increasing risks relative to the more common <i>APOE3</i> allele. In this study, we investigated the impacts of the <i>APOE</i> genotype on systemic and neural effects of the Western diet. Female mice with knock-in of human <i>APOE3</i> or <i>APOE4</i> were exposed to control or Western diet for 13 weeks. In the control diet, we observed that <i>APOE4</i> mice presented with impaired metabolic phenotypes, exhibiting greater adiposity, higher plasma leptin and insulin levels, and poorer glucose clearance than <i>APOE3</i> mice. Behaviorally, <i>APOE4</i> mice exhibited worse performance in a hippocampal-dependent learning task. In visceral adipose tissue, <i>APOE4</i> mice exhibited generally higher expression levels of macrophage- and inflammation-related genes. The cerebral cortex showed a similar pattern, with higher expression of macrophage- and inflammation-related genes in <i>APOE4</i> than <i>APOE3</i> mice. Exposure to the Western diet yielded modest, statistically non-significant effects on most metabolic, behavioral, and gene expression measures in both <i>APOE</i> genotypes. Interestingly, the Western diet resulted in reduced gene expression of a few macrophage markers, specifically in <i>APOE4</i> mice. The observed relative resistance to the Western diet suggests protective roles of both female sex and young adult age. Further, the data demonstrate that <i>APOE4</i> is associated with deleterious systemic and neural phenotypes and an altered response to a metabolic stressor, findings relevant to the understanding of interactions between the <i>APOE</i> genotype and risks for metabolic disorders. |
| first_indexed | 2024-03-11T08:26:47Z |
| format | Article |
| id | doaj.art-f1a1e401f27a473ebe74a9c768bdd401 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T08:26:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-f1a1e401f27a473ebe74a9c768bdd4012023-11-16T22:05:28ZengMDPI AGMetabolites2218-19892023-02-0113228710.3390/metabo13020287Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female MiceAmy Christensen0Christian J. Pike1Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USADavis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USAWestern diets high in sugars and saturated fats have been reported to induce metabolic and inflammatory impairments that are associated with several age-related disorders, including Alzheimer’s disease (AD) and type 2 diabetes (T2D). The apolipoprotein E (<i>APOE</i>) genotype is associated with metabolic and inflammatory outcomes that contribute to risks for AD and T2D, with the <i>APOE4</i> genotype increasing risks relative to the more common <i>APOE3</i> allele. In this study, we investigated the impacts of the <i>APOE</i> genotype on systemic and neural effects of the Western diet. Female mice with knock-in of human <i>APOE3</i> or <i>APOE4</i> were exposed to control or Western diet for 13 weeks. In the control diet, we observed that <i>APOE4</i> mice presented with impaired metabolic phenotypes, exhibiting greater adiposity, higher plasma leptin and insulin levels, and poorer glucose clearance than <i>APOE3</i> mice. Behaviorally, <i>APOE4</i> mice exhibited worse performance in a hippocampal-dependent learning task. In visceral adipose tissue, <i>APOE4</i> mice exhibited generally higher expression levels of macrophage- and inflammation-related genes. The cerebral cortex showed a similar pattern, with higher expression of macrophage- and inflammation-related genes in <i>APOE4</i> than <i>APOE3</i> mice. Exposure to the Western diet yielded modest, statistically non-significant effects on most metabolic, behavioral, and gene expression measures in both <i>APOE</i> genotypes. Interestingly, the Western diet resulted in reduced gene expression of a few macrophage markers, specifically in <i>APOE4</i> mice. The observed relative resistance to the Western diet suggests protective roles of both female sex and young adult age. Further, the data demonstrate that <i>APOE4</i> is associated with deleterious systemic and neural phenotypes and an altered response to a metabolic stressor, findings relevant to the understanding of interactions between the <i>APOE</i> genotype and risks for metabolic disorders.https://www.mdpi.com/2218-1989/13/2/287apolipoprotein Ebehaviorinflammationmetabolic stressobesogenic diet |
| spellingShingle | Amy Christensen Christian J. Pike Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice Metabolites apolipoprotein E behavior inflammation metabolic stress obesogenic diet |
| title | Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice |
| title_full | Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice |
| title_fullStr | Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice |
| title_full_unstemmed | Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice |
| title_short | Effects of <i>APOE</i> Genotype and Western Diet on Metabolic Phenotypes in Female Mice |
| title_sort | effects of i apoe i genotype and western diet on metabolic phenotypes in female mice |
| topic | apolipoprotein E behavior inflammation metabolic stress obesogenic diet |
| url | https://www.mdpi.com/2218-1989/13/2/287 |
| work_keys_str_mv | AT amychristensen effectsofiapoeigenotypeandwesterndietonmetabolicphenotypesinfemalemice AT christianjpike effectsofiapoeigenotypeandwesterndietonmetabolicphenotypesinfemalemice |