6 research outputs found
Effects of Maresin 1 (MaR1) on Colonic Inflammation and Gut Dysbiosis in Diet-Induced Obese Mice
The aim of this study was to characterize the effects of Maresin 1 (MaR1), a DHA-derived
pro-resolving lipid mediator, on obesity-related colonic inflammation and gut dysbiosis in diet-induced
obese (DIO) mice. In colonic mucosa of DIO mice, the MaR1 treatment decreased the expression
of inflammatory genes, such as Tnf-α and Il-1β. As expected, the DIO mice exhibited significant
changes in gut microbiota composition at the phylum, genus, and species levels, with a trend to a
higher Firmicutes/Bacteroidetes ratio. Deferribacteres and Synergistetes also increased in the DIO
animals. In contrast, these animals exhibited a significant decrease in the content of Cyanobacteria
and Actinobacteria. Treatment with MaR1 was not able to reverse the dysbiosis caused by obesity
on the most abundant phyla. However, the MaR1 treatment increased the content of P. xylanivorans,
which have been considered to be a promising probiotic with healthy effects on gut inflammation.
Finally, a positive association was found between the Deferribacteres and Il-1β expression, suggesting
that the increase in Deferribacteres observed in obesity could contribute to the overexpression of
inflammatory cytokines in the colonic mucosa. In conclusion, MaR1 administration ameliorates
the inflammatory state in the colonic mucosa and partially compensates changes on gut microbiota
caused by obesity
Effects of Maresin 1 (MaR1) on Colonic Inflammation and Gut Dysbiosis in Diet-Induced Obese Mice
The aim of this study was to characterize the effects of Maresin 1 (MaR1), a DHA-derived
pro-resolving lipid mediator, on obesity-related colonic inflammation and gut dysbiosis in diet-induced
obese (DIO) mice. In colonic mucosa of DIO mice, the MaR1 treatment decreased the expression
of inflammatory genes, such as Tnf-α and Il-1β. As expected, the DIO mice exhibited significant
changes in gut microbiota composition at the phylum, genus, and species levels, with a trend to a
higher Firmicutes/Bacteroidetes ratio. Deferribacteres and Synergistetes also increased in the DIO
animals. In contrast, these animals exhibited a significant decrease in the content of Cyanobacteria
and Actinobacteria. Treatment with MaR1 was not able to reverse the dysbiosis caused by obesity
on the most abundant phyla. However, the MaR1 treatment increased the content of P. xylanivorans,
which have been considered to be a promising probiotic with healthy effects on gut inflammation.
Finally, a positive association was found between the Deferribacteres and Il-1β expression, suggesting
that the increase in Deferribacteres observed in obesity could contribute to the overexpression of
inflammatory cytokines in the colonic mucosa. In conclusion, MaR1 administration ameliorates
the inflammatory state in the colonic mucosa and partially compensates changes on gut microbiota
caused by obesity
GLUT12 expression in brain of mouse models of Alzheimer's Disease
The brain depends on glucose as a source of energy. This implies the presence of glucose transporters, being GLUT1 and GLUT3 the
most relevant. Expression of GLUT12 is found in mouse and human brain at low levels. We previously demonstrated GLUT12
upregulation in the frontal cortex of aged subjects that was even higher in aged Alzheimer’s disease (AD) patients. However, the cause
and the mechanism through which this increase occurs are still unknown. Here, we aimed to investigate whether the upregulation of
GLUT12 in AD is related with aging or Aβ deposition in comparison with GLUT1, GLUT3, and GLUT4. In the frontal cortex of two
amyloidogenic mouse models (Tg2576 and APP/PS1) GLUT12 levels were increased. Contrary, expression of GLUT1 and GLUT3
were decreased, while GLUT4 did not change. In aged mice and the senescence-accelerated model SAMP8, GLUT12 and GLUT4
were upregulated in comparison with young animals. GLUT1 and GLUT3 did not show significant changes with age. The effect of βamyloid (Aβ) deposition was also evaluated in Aβ peptide i.c.v. injected mice. In the hippocampus, GLUT12 expression increased
whereas GLUT4 was not modified. Consistent with the results in the amyloidogenic models, GLUT3 and GLUT1 were downregulated. In summary, Aβ increases GLUT12 protein expression in the brain pointing out a central role of the transporter in AD
pathology and opening new perspectives for the treatment of this neurodegenerative disease
Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice
Objective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties.
Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning.
Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes.
In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6 / ) mice.
Results: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose
uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial
biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown
adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling,
characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic
activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT
activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates
Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in
Il6 / mice.
Conclusions: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in
adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes,
and that IL-6 is required for the thermogenic effects of MaR1