So similar to the gut-brain axis, there is also the adipose tissue-brain axis!
It is not uncommon for peripheral tissues to be involved in regulating brain function.
Animal studies have shown that restoring the glucose metabolism of bone marrow cells can reverse the cognitive decline caused by aging; the intestinal vagus nerve is involved in the hippocampus-dependent episodic and spatial memory of animals; the liver plays an important role in the feeding behavior of mice…
Fat (photoAC)
Similarly, studies have found that adipose tissue may also be involved in regulating brain function.
To gain insight into the link between fat and the brain, the researchers performed a transcriptomic analysis of visceral adipose tissue from 17 obese subjects, aged 28-60 years, with a BMI >35. The researchers then tested their cognitive performance in memory, executive function and attention.
Among all the genes, NUDT2, AMPH, UNC5B, and OAT were most significantly associated with cognition. NUDT2 mutations are associated with intellectual disability, AMPH encodes one of the proteins significantly altered in mild cognitive impairment and Alzheimer’s disease, and OAT encodes ornithine aminotransferase, which plays an important role in neurotransmitter synthesis.
Although their central function is originally related to cognition, this is the first time their expression in adipose tissue has been found to be related to cognition.
In another cohort, 22 obese subjects aged 23-57 were included who underwent the same cognitive tests and had RNA-sequencing of visceral and subcutaneous fat.
Combining the findings of the two cohorts and screening for genes associated with at least one of the three cognitive domains, a total of 188 overlapping genes were found with significant roles in synaptic function and inflammatory pathways.
Using partial least squares analysis (PLS), the researchers tried to find the mechanism behind adipose tissue and cognition. Analysis results showed that phospholipid metabolism, inflammatory response, vitamin A metabolism, and synaptic function were potential mechanistic explanations.
The researchers tested the specific power of the lipid-brain axis in fruit flies. They down-regulated AMPH, UNC5B, NUDT2, OAT, NR4A2/NR4A3 and EZR homologues Amph, unc-5, Datp, Oat, Hr38 and Moe in the Drosophila fat body. As can be seen in the figure below, the learning index of Drosophila ( LI) showed significant changes.
In the first two cohorts, the genes RIMS1 and SLC18A2 involved in neurotransmitter release had the most significant associations with different cognitive domains.
Downregulation of SLC18A2 in mouse adipose tissue alone significantly reversed high-fat diet-induced cognitive impairment, while overexpression of RIMS1 ortholog Rim in Drosophila also led to improved learning ability.
Since the cohort of the study mainly involves obese people with a BMI>35, the above conclusions may not be extended to the general population. It would be great if there is a larger-scale study in the future.
Brain (photoAC)
However, at least we can conclude that the adipose tissue-brain axis does exist, and the impact is quite obvious. Perhaps in the future, we can treat brain problems by targeting adipose tissue drug delivery, and the safety should be guaranteed. Various genes and their products mentioned in the study can also play a role as potential biomarkers.
References:
[1]https://www.science.org/doi/full/10.1126/sciadv.adg4017
2023-08-31 09:14:29
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