Abstract: Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression.
Moreover, functional TLR4 is required for the development of high-fat diet-induced
obesity. Recently, central alterations in TLR4 expression have been associated with the
modulation of visceral pain. However, it remains unknown whether there is a functional
interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present
study we investigated the impact of long-term exposure to high-fat diet on visceral pain
perception and on the levels of TLR4 and Cd11b (a microglial cell marker) protein expression
in the prefrontal cortex (PFC) and hippocampus. Peripheral alterations in TLR4 were
assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we
evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a
selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced
visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation
were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise,
peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting
in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted
the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a
role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to
TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity
present in pathologies associated to fat diet consumption.
Fuente: PLoS ONE 11 (5): e0155367
Editorial: Public Library of Science
Año de publicación: 2016
Nº de páginas: 15
Tipo de publicación: Artículo de Revista
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MONICA TRAMULLAS FERNANDEZ
FINGER, BEATE C.
DINAN, TIMOTHY G.
CRYAN, JOHN F.