Table 2.
Mixed or saturated HFD effects on synaptic function and cognition in animals.
| Exp. Approach | Species, Sex, Age | Model | Learning/Memory | Synaptic Function, Neuroplasticity | Other Pathways | Refs. |
|---|---|---|---|---|---|---|
| Days (≤2 weeks) | ||||||
| Young animals | Rat (♂; 3 w & 2 m) | Saturated HFD (F: 60% & C: 20%) vs. CD (C: 35%) for 7 days | Impaired long-term memory (NLR) in young animals but improved in old ones. No changes in short-term memory | ↓ LTP in CA1-HPC in young animals, but ↑ in old ones | ↑ glucocorticoids release in young animals | [103] |
| Mouse (♂; 5 w) | HFD (F: 45% & C: 35%) vs. CD (F: 18% & C: 58%) for 2 days | - | ↓ LTP in HPC. No changes in LTD | - | [104] | |
| Mouse (♂; 6 w) | HFD (F: 60% & C: 27%) vs. CD (F: 10% & C: 70%) for 1 to 7 days | Impaired memory (NOR) at 3–7 days | ↓ synaptophysin at 7 days in HPC. No changes at 3 days | ↑ BBB permeability at 1–3 days (no changes at 4–6 days) and inflammation at 2 days (no changes at 1 or 3–7 days) | [105] | |
| Mouse (♂; 6 w) | HFD (F: 60% & C: 21%) vs. CD (F: 13% & C: 67%) for 7 days | - | ↓ BDNF and dendritic tree in HPC | - | [106] | |
| Adult animals | Rat (♂) | Saturated HFD (F: 48% & C: 37%) or PUFA HFD (F: 46% & C: 37%) vs. CD (F: 21% & C: 56%) for 2 w | Impaired memory (NLR) with saturated. No changes with PUFA | No changes in BDNF in HPC | Gut dysbiosis. No changes in inflammation in HPC | [100] |
| Mouse (♂; 10 w) | HFD (F: 30% by weight) vs. CD (F: 5% by weight) for 7 days | Impaired memory (NOR, Y-maze & temporal order memory test) | ↓ PSD95, BDNF, thickened of post synaptic density, & ↑ width of synaptic cleft in HPC & PFC | Gut dysbiosis, ↑ microglia activation, & inflammation in HPC & PFC | [93] | |
| Mouse (♂; 12 w) | Saturated HFD (F: 60%) vs. CD (F: 10%) in animals for 3 days, 1 or 2 w | - | - | Alterations in metabolism, cell stress, inflammation, cell signaling & cytoskeleton | [107] | |
| Young vs. aged animals | Rat (♂; 3 m & 24 m) | Mixed HFD (F: 60.3% & C: 21.3%) vs. CD (F:17% & C: 54%) for 3 days | Impaired long-term memory (FC & MWM) in aged animals. No changes in short-term memory or in young animals | - | ↑ microglia activation & inflammation in aged animals in HPC & amygdala | [92] |
| Rat (♂; 3 m & 24 m) | Mixed HFD (F: 60.3% & C: 21.3%) vs. CD (F:17% & C: 54%) for 3 days | - | - | ↑ inflammation in microglia of young & old animals in HPC & amygdala | [108] | |
| Short periods (>2 weeks and ≤2 months) | ||||||
| Young animals | Rat (♂; 3 w) | Mixed HFD (F: 42% & C: 25%) or CD (F: 4% & C: 50%) for 7 w | - | ↓ GluA2, PSD95, synaptophysin, & TrKB receptor in HPC. No changes in BDNF | ↓ glucocorticoid receptor in HPC | [109] |
| Mouse (♂; 3 w) | HFD (F: 60%) vs. CD (F: 6.55%) for 8 w | - | ↓ response to leptin induction of AMPAR-mediated synaptic transmission in HPC neurons | - | [110] | |
| Mouse (♂; 3 w) | HFD (F: 21.2% & C: 22.5% by weight) & CD (F:3.6% & C: 28.8% by weight) for 6 w | Impaired memory (NOR) | Synaptic loss in CA1-HPC neurons | ↓ neurogenesis and ↑ inflammation in HPC | [111] | |
| Mouse (♂; 8 w) | HFD (F: 60% & C: 20%) calorically matched or ad libitum vs. CD (F: 13% & C: 58%) for 3 w. | - | ↓ spine density in PFC in both HFD protocols | - | [112] | |
| Mouse (♂; 4 w) | Saturated HFD (F: 60%) vs. CD (F: 6.55%) for 6–7 w | Impaired memory (MWM) | ↓ LTP in HPC. ↓ GluA1 phosphorylation & ↑ palmitoylation in HPC | INS resistance in HPC | [32] | |
| Mouse (♂; 4 w) | Saturated HFD (F: 60%) vs. CD (F: 6.55%) for 6–7 w | Impaired memory (NOR & NLR) | ↓ BDNF, phosphoTRKB, phosphoCREB & glutamate metabotropic receptors in HPC | - | [113] | |
| Mouse (♂; 5 & 8 w) | SOLF (60% CD + 40% saturated oil-enriched food) or UOLF (60% CD + 40% unsaturated oil-enriched food) for 8 w | Impaired memory (Y-maze) by SOLF | ↓ GluN2A & 2B by SOLF/UOLF in young animals (no changes in old). ↓ LTP & ↑ LTD by SOLF in young animals | - | [102] | |
| Rat (♂; 6 w) | HFD (F: 40%) vs. CD for 6 w | Impaired learning & memory (MWM) | - | ↑ ER stress & INS resistance in HPC | [114] | |
| Rat (♂; 7 w) | HFD (F: 40% & C: 40%) vs. CD (F: 12.5% & C: 62.9%) for 8 w | - | ↓ BDNF in PFC | ↑ ER stress in PFC | [115] | |
| Rat (♂; 2 m) | HFD (5000 kcal/kg) vs. CD (3600 kcal/kg) for 8 w | Impaired learning & memory (MWM) | ↓ synaptotagmin1 & synapsin 1 | - | [116] | |
| Mouse (♂; 6–8 w) | HFD (F: 21.2% & C: 61.3% by weight) vs. CD (F: 7.5% & C: 75.1% by weight) for 4 or 7 w | Impaired long-term memory (FC). No changes in short-term memory (NLR) | ↓ LTP in CA1-HPC. ↓ cfos, synaptophysin, CaMKII & IV, calcineurin A in HPC. No changes in BDNF | ↑ oxidative stress | [117] | |
| Mouse (♂; 8 w) | HFD (F: 45%) vs. CD (F: 10%) for 2 m | Impaired short-term memory (T-maze) | - | INS resistance in brain | [118] | |
| Adult animals | Rat (♂; adult) | HFD (F: 58% & C: 17%) vs. CD for 5 w | Impaired learning & memory (MWM) | - | - | [119] |
| Rat (♂) | HFD (F: 20% & C: 48% by weight) vs. CD (F: 5% & C: 47% by weight) for 8 w | - | No changes in LTP in DG-HPC | - | [120] | |
| Rat | Mixed HFD (F: 39%) vs. CD (F: 13%) for 2 m | - | - | ↑ oxidative stress | [121] | |
| Rat (♂; 16 m) | Saturated HFD (2 % cholesterol + 10 % trans coconut oil) vs. soybean oil (12%) for 8 w | Impaired memory (water radial arm maze) | Dendritic loss in HPC | ↑ microglia activation & inflammation in HPC | [101] | |
| Mouse (♂) | Mixed HFD (F: 45% & C: 45%) vs. CD (F: 10% & C: 70%) for 8 w | No changes in memory (Y-maze & NOR) | - | - | [122] | |
| Long periods (>2 months) | ||||||
| Young animals | Mouse (♂; 4 w) | Mixed HFD (F: 60% & C: 20%) vs. SD (F: 10% & C: 70%) for 14 w | Impaired memory (Y-maze & MWM) | ↓ BDNF in HPC & CTX | Altered antioxidant defense, ↑ oxidative stress, inflammation & INS resistance in HPC & CTX | [123] |
| Rat (♂; 5–6 w) | HFD (F: 59.28%) vs. CD (F: 19.77%) for 16 w | Impaired memory (MWM) | ↓ spine density & LTP in HPC | INS resistance & ↓ mitochondrial function in brain | [124] | |
| Rat (♂; 6 w) | Mixed HFD (F: 60% & C: 20%) vs. CD (F: 13% & C: 58%) for 6 m | Impaired learning (FC) | ↑ surface GluA1 in HPC. No changes in total levels or GluN2B | - | [125] | |
| Mouse (♂; 6 w) | Mixed HFD (F: 60%) vs. CD (F: 12.6%) for 16 w | Impaired memory (Y-maze) | ↓ GluN1/2A, GluA1, PSD95 & synaptophysin. No changes in GluN2B or GluA2 | - | [126] | |
| Mouse (♂; 6 w) | HFD (F: 22% by weight) vs. CD (F: 6% by weight) for 16 w | - | - | ↑ inflammation in HPC & CTX & gliosis in CTX | [127] | |
| Rat (♂; 7 w) | Mixed HFD (F: 45%) vs. CD (F: 6%) for 17 w | - | ↓ PSD95. No changes in synaptophysin | - | [128] | |
| Mouse (♂; 8 w) | Saturated HFD (F: 59% & C: 26%) vs. CD (F: 11% & C: 59%) for 8, 16, 24 & 28 w | No changes in short-term (Y-maze), long-term & learning (MWM). Impaired cognitive flexibility | - | No changes in microglia activation in HPC & CTX | [129] | |
| Mouse (♂; 8 w) | Mixed HFD (F: 60% & C: 20%) vs. CD (F: 10% & C 70%) for 46 w | Impaired memory (MWM, NOR & Y-maze) | ↓ branching, spine density, PSD95, spinophilin, & synaptophysin in HPC | ↑ microglia activation, inflammation & iNOS in HPC | [130] | |
| Mouse (♂; 8 w) | Mixed HFD (F: 60%) vs. CD for 16 w | Impaired learning & memory (MWM) | - | ↑ inflammation & INS resistance in HPC & CTX | [131] | |
| Mouse (♂; 8–10 w) | Mixed HFD (F: 45%) vs. CD (F: 10% & C: 60%) for 13 w | - | ↓ synaptophysin in HPC | ↑ oxidative stress & INS resistance, & ↓ neurogenesis in HPC | [132] | |
| Mouse (♀; 2 m) | Mixed HFD (F: 60%) vs. CD (F: 10%) for 4 m. Intervention: 16 m with CD | Impaired learning & memory (MWM & FC) | ↓ BDNF in HPC | No changes in inflammation or mitochondrial function in HPC | [95] | |
| Adult animals | Mouse (♂) | HFD (F: 45%) vs. CD (F: 10%) for 17 w | Impaired memory (T-maze) | ↓ LTP in HPC | - | [96] |
| Mouse (♂; 9 w) | HFD (F: 60% by weight) vs. CD (F: 5% by weight) for 13–15 w | Impaired memory (NOR & NLR) | ↓ BDNF, synaptophysin, & PSD95 in HPC & PFC | Gut dysbiosis, ↑ inflammation, & microglia activation in HPC & PFC | [97] | |
| Mouse (♂; 9 w) | Mixed HFD (F: 60% & C: 20%) vs. CD (F: 10% & C: 70%) for 24 w | Impaired memory (MWM & Y-maze) | ↓ PSD95 & SNAP23 in HPC & CTX | ↑ inflammation, microglia activation, oxidative stress, INS resistance & Aβ in HPC & CTX | [98] | |
| Mouse (♂; 12 w) | HFD (F: 55%) vs. CD (F: 13%) for 15 w | Impaired memory (NOR & NLR) | ↓ PSD95, synaptophysin, thickened of post synaptic density, & ↑ width of synaptic cleft in CA1-HPC | Gut dysbiosis, ↑ inflammation, microglia activation, & INS resistance in CA1-HPC | [99] | |
Mixed or saturated HFD effects were classified according to experimental approach, taking into account exposure time, days (≤2 weeks), short (>2 weeks and ≤2 months) or long (>2 months) periods, sex, and age classified as young and adult (≤2 months, >2 months). Search terms used were as follows: “high fat diet” AND “learning”, “memory”, “synaptic plasticity” OR “AMPAR”. Only studies with rodents were included. Excluded were experimental models of maternal exposure. Percentage fats, carbohydrates, and proteins are relative to total energy unless otherwise indicated. Table abbreviations (used for the first time in this table) are as follows: Aβ: amyloid-β; DG: dentate gyrus; iNOS: inducible nitric oxide synthase; and SNAP23: synaptosome-associated protein 23.