Tanycyte BMAL1 regulates high-fat diet weight gain and shapes arcuate neurogenesis in female mice.

Oxidative stress is slowly
growing to the rank of a civilization
disease. It often results from a poor diet, consumption of highly
processed food, excessive use of stimulants, and prolonged stress.
One of the consequences of uncontrolled oxidative stress, i.e., the
lack of a balance between the level of oxidants and antioxidants,
is damage to cells, tissues, and organs caused by oxidative damage.
The brain, with its high oxygen consumption and lipid-rich content,
is highly susceptible to oxidative stress. Excessive damage to biomolecules due to oxidation stress leads to
cellular malfunction and neurodegeneration. Several
neurological disorders, including Alzheimer’s, Parkinson’s,
Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke,
are associated with oxidative stress. Interestingly, cell membranes
in brain constitute greater than 66% phospholipids by mass, indicating that the oxidative stress effect on
membranes should be systematically investigated. As the basic
building blocks of cell membranes are lipid molecules,
it is justified to investigate how they are affected by oxidation
stress. The oxidation of lipids is a complex process in which oxidants
(such as free radicals or reactive oxygen species) attack lipid molecules
containing carbon double bonds (unsaturated). This leads to the degeneration of acyl chains of lipids (commonly
known as rancidity), disruption of their functions, and the formation
of peroxide and hydroperoxide derivatives. There exist several studies
that focus on the effect of oxidation of lipids on the behavior and
properties of lipid membrane models. Phenomena such as the increase in membrane surface area, decrease
of membrane thickness, promotion of lipid domain formation, change
in lipid order, and formation of transient pores affecting membrane
permeability were observed. However, the membrane lipid composition
is tightly regulated by the cell, maintaining a homeostasis that,
if disrupted, can impair cell function and lead to disease. Furthermore,
oxidative stress might also indirectly influence the membrane composition
and homeostasis. For instance, the increased oxidative stress in the
hippocampus has led to an increase in the amount/activity of sphingomyelinase
and thus an increase in the production of ceramides. It was even hypothesized that it can affect cell delivery
and affect the function of membrane peptides. As a result, simple lipid models, composed of one or two lipid molecules,
might not be sufficient to grasp the in-depth effect of oxidation
on the membranes itself. Fortunately, the recent development of lipidomics
allows the determination of detailed lipid composition and hence allowed
the emergence of biomimetic lipid membranes. In this article, such an approach was used. Specifically,
the composition
of the membrane investigated in this study was based on ratios presented
for human brain tissue, superficially an inner membrane of human neurons. However, a bottom-up approach was used: starting
from a simple homogeneous membrane, additional lipid types are added
and the impact on membrane properties is investigated. Combined computational
and experimental studies of lipid membranes were carried out to determine
the change of membrane properties due to the presence of oxidized
lipid molecules.