The document summarizes research into how a furanone compound from marine origins can reduce lipid accumulation in cells in vitro by targeting the LXRα and PPARα nuclear receptors. The study used techniques like fluorescent immunocytochemistry, Western blotting, qPCR, and cell viability assays to examine the compound's effects on receptor expression and activity, as well as lipid levels. Results demonstrated that the furanone enhanced proteins involved in cholesterol efflux like ABCA1 and ABCG1 while increasing LXRα and PPARα expression. This suggests it lowers lipids by influencing multiple metabolic pathways regulated by these receptors. The conclusions discuss the compound's potential natural therapeutic application for hyperlipidemia by modulating the important

1. Presentado por: Juliana Téllez Gómez

2. Introduction
PPARα
Peroxisome proliferator-activated
receptors (PPARs) including three
sub-family members, PPARα,
PPARβ/δ and PPARγ, are nuclear
receptors that regulate lipid
metabolism via their
transcriptional activity.
LXRα
Liver X receptors (LXRs) are kind
of nuclear receptor that plays key
roles in the regulation of lipid
metabolism.
The LXRs are activated by
endogenous ligands such as
oxysterols, intermediate precursors
in the cholesterol biosynthetic
pathway such as desmosterol.
2

3. 3
Introduction
Furanone
Is considered as one of the pharmaophores of biologically
active substances. The furanone named as 5-hydroxy-3-
methoxy-5-methyl-4-butylfuran-2(5H) one had an effective
lipid-lowering activity via influencing multiple processes of
lipid metabolism.
Furanone is present in lots of natural products including food
and has been reported to have various biological functions
such as anticancer, antiviral, antifungal, antibacterial, anti-
inflammatory, antioxidant, antiarthritic and anti-
hyperlipidaemic.

4. Objetive
Relate how furanone of marine origin reduces the
accumulation of intracellular lipids in vitro by
targeting LXRα and PPARα.
4

5. Methods
Fluorescent immunocytochemistry assay
Immunostaining technique that makes use of antibodies chemically
bound to a fluorescent substance to demonstrate the presence of a
particular molecule.
It is based on the high specificity and high affinity that antibodies have to
recognize molecules and bind to them. In addition, the conjugation or
combination of antibodies with enzymes or fluorescent substances allows
to detect amounts of molecules present in the tissue.
5

6. Protein isolation, electrophoresis and Western blotting.
It is a laboratory technique used to detect a specific protein in a blood
or tissue sample. The method involves the use of gel electrophoresis
to separate the proteins from the sample. The membrane is exposed
to a specific antibody against the protein under study. Antibody
binding is detected using a radioactive or chemical label.
Methods
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7. Methods
Real-time quantitative PCR
It is based on the natural property of DNA
polymerases to replicate strands of DNA,
for which alternating high and low
temperature cycles are used to separate
newly formed strands of DNA from each
other after each replication phase and then
let the strands of DNA come back together
to duplicate them again.
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8. Methods
8
Cell viability assay
It is based on the metabolic
reduction of 3- (4,5 dimethylthiazol-
2-yl) -2,5-diphenyltetrazole (MTT)
bromide made by the mitochondrial
enzyme succinate dehydrogenase in
a blue colored compound, directly
will determine the mitochondrial
functionality of the treated cells.
This method has been widely used
to measure survival and cell
proliferation.

9. Results
9
Typical pictures of Oil Red O staining (100 ×)

10. 10
Results
Effect of the
furanone
on enhancing
the protein
expression of
ABCA1, ABCG1
and SR-B1 in
RAW264.7
cells.

11. 11
Results
Effect of
furanone on the
protein
expression of
LXRs and the
effect
of LXR
antagonists on
furanone-
induced
protein

12. 12
Results
Protein expression of PPARα densitometric quantification

13. Discussion
13
Author Quote Yes or No
Furthermore, SR9243
showed no effect on the TG
accumulation in zebrafish
hepatocytes.
Pan YX, et al.
SREBPs are important
transcription factors
involved in the regulation of
lipid metabolism and
homeostasis in the liver.
Moslehi A, et al.
The underlying
mechanisms may be similar
to those of LXR
antagonists.
Griffett K, et al

14. Conclusions
14
Hyperlipidemia is one of the
most frequent and common
diseases in today's society due
mainly to unhealthy lifestyle
habits. Every day it is sought
that the medications with
which this disease is treated
have fewer side effects and are
more natural as is the case
with furanone.
The LXRα and PPARα
receptors are essential in
lipid metabolism, and it is
for this reason that their
mechanism of action must
be known, how they are
activated and what role they
play in atherosclerotic
disease.

15. 15