Table 3 Effects of diet on microglia

Mice

Hypothalamus and total brain

LFD (6.5% fat), HFD (42% fat) and caloric restriction (40% less) for 6 and 24 months

HFD increased the number of microglia in the hypothalamus and both number and soma size of microglia were increased in the cerebellum during aging in HFD mice. Under basal- or LPS-induced inflammatory conditions, gene expression analysis of the total brain microglia population or hypothalamus tissue showed similar findings in HFD and LFD mice. Caloric restriction in LFD mice prevented the increased expression of phagocytic markers in white matter microglia with aging, and this protective effect of caloric restriction was not observed in HFD mice. Because running wheel access did not affect white matter microglia activation in either diet, dietary fat as well as caloric content may play an important role in the inflammatory process in brain aging

[123]

Mice

Hypothalamus

Standard diet (13,2% fat) or HFD (42% fat) for 28 days

HFD led to microglial reactivity and neuronal stress in the mediobasal hypothalamus. Microglial depletion abrogated HFD-induced hypothalamic inflammation besides to enhance leptin signalling and reduce food intake

[147]

Mice

Hippocampus and amygdala

HFD (60.3% fat) for 3 days

In the hippocampus, HFD induced enlarged synaptophysin boutons, indicative of neurodegeneration. In the amygdala, HFD exacerbated the effects of ageing on microglial priming (morphology) and significantly suppressed microglial phagocytosis

[115]

Mice

White matter

Western diet (42% fat)

WD diet induced an ageing-related metabolic dysfunction associated with impaired myelin-debris clearance in microglia, which is mediated by TGF-β signalling and disrupts lesion recovery after demyelination. Blocking TGF-β restores microglia responsiveness and myelin-debris clearance following demyelinating injury

[148]

Mice

Nucleus accumbens

high-caloric chocolate cafeteria diet for 43 days

This high-caloric diet led to microglial reactivity with increased expression of pro-inflammatory factors and abnormal responses after amphetamine-induced hyperlocomotion. Chronic inhibition of microglial reactivity normalised these behavioural alterations

[149]

Mice and Human

Hypothalamus

Mice: HFD (60% fat) for 8 weeks

Human: post-mortem samples from obese individuals (BMI > 30)

HFD induced microglia number in the hypothalamus of mice. Gene expression analysis of isolated microglia found downregulation of genes important for sensing signals in microenvironment. In obese humans, it was found signs of hypothalamic gliosis and exacerbated microglial dystrophy

[111]

Mice

Hippocampus

HFD (60% fat) for 8 weeks

HFD partially disrupted the rhythmicity of circadian clock genes in microglia, besides disruption on microglial immune gene expression. HFD induced a shift of substrate utilisation on microglia, with decreased glutamate and glucose metabolism and an overall increase of lipid metabolism during active period of the animals

[150]

Mice

Hypothalamus

Caloric restriction (40% of the ad libitum food intake) in HFD and LFD animals for 23 months

Caloric restriction in combination with LFD affected microglial morphology and decreased expression of phagocytic markers (Mac2/Lgals3, Dectin-1/Clec7a and CD16/CD32 in microglia

[123]

Mice

Hippocampus

Luteolin intake (20 mg/d) for 4 weeks

In aged animals, luteolin food supplement improved spatial memory and restored expression of inflammatory markers compared with that of young animals

[131]

Rat

-

EO and EP intake (2%) for 8 weeks

In aged animals, this diet improved working memory. Then, blood serum was used to assess microglial response in vitro. BV-2 microglia treated with blood serum from EO- and EP-fed rat showed reduced expression of NO and TNF-α respectively

[133]

Mice

Hippocampus

HFD and LFD with or without blueberry (4%) for 5 months

HFD supplemented with blueberry had fewer microglia compared to LFD and HFD ones. BV-2 microglia treated with serum collected from mice fed the diets with blueberry produced less NO compared to HFD mice. HFD + blueberry mice presented higher levels of hippocampal BDNF and DCX-positive cells compared to mice fed HFD

[139]

Mice

Frontal cortex

Caloric restriction (70% of the ad libitum food intake) for 6 weeks and 6 and 12 months

Caloric restriction for 6- and 12 months counteracted ageing-induced microglial changes such as Ca²⁺ signalling and processes motility toward a younger phenotype. Even shot-term caloric restriction (6 weeks) beginning in old age significantly improved microglial motility and Ca²⁺ signalling

[124]