Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models

Abstract

Obesity induces inflammation both in the adipose tissue and the brain. Activated macrophage infiltration, polarization of macrophages to a more inflammatory type (M1), and increased levels of pro-inflammatory cytokines are related to brain inflammation, which induces leptin resistance in the brain. Pyrogallol-phloroglucinol-6,6-bieckol (PPB), a compound from Ecklonia cava, has anti-inflammatory effects. In this study, we evaluated the effects of PPB effect M1 polarization and inflammation and its ability to restore the effects of leptin, such as a decrease in appetite and body weight. We administered PPB to diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice, evaluated macrophage activation, polarization, and changes of inflammatory cytokine level in adipose tissue and brain, and determined the effect of PPB on leptin resistance or leptin sensitivity in the brain. The levels of activated macrophage marker, M1/M2, and pro-inflammatory cytokines were increased in the adipose tissue and brain of DIO and ob/ob mice than control. TLR4 expression, endoplasmic reticulum (ER) stress, and NF-κB expression in the brain of DIO and ob/ob mice were also increased; this increase was related to the upregulation of SOCS3 and decreased phosphorylated STAT3, which decreased leptin sensitivity in the brain. PPB decreased inflammation in the brain, restored leptin sensitivity, and decreased food intake and weight gain in both DIO and ob/ob mice.

The Phlorotannin-Rich Fraction ofEcklonia cavaExtract Attenuated the Expressions of the Markers Related with Inflammation and Leptin Resistance in Adipose Tissue

“…Decreased ObR protein and mRNA expression and localization on adipocyte surfaces are key determinants of cell sensitivity to leptin [15]. Interestingly, PPB also restored leptin sensitivity in HFD-induced obese mice and ob/ob mice [55]. We also found that ECE inhibited HFD-induced decreases in ObR expression, which suggests that ECE enhanced adipocyte leptin sensitivity by maintaining ObR expression ( Figures 5(f )-5(h)).…”

Brown Seaweed Food Supplementation: Effects on Allergy and Inflammation and Its Consequences

“…Polyphenols were demonstrated to be very well capable of suppressing the increase of TLRs, including TLR4 [ 124 , 126 , 127 ], TLR2 [ 124 , 127 ] and TLR7 [ 124 ]. TLRs as primary sensors of microbial products activate signaling pathways that lead to the induction of immune- and inflammatory genes, such as the NF-κB pathway.…”

Alzheimer’s Disease and Diabetes: Role of Diet, Microbiota and Inflammation in Preclinical Models

“…In line with these observations, elevated TNF-α levels lead to a decrease in Azgp1 mRNA and protein levels in adipose tissues of ob/ob mice [ 177 , 192 ]. Additionally, IL-6, TNF-α [ 195 , 196 , 197 ], IL-1β, IL-10 [ 193 ] and plasminogen activator inhibitor-1 (PAI-1) are increased in the adipose tissue and the spleen of ob/ob mice [ 195 , 197 ]. IFN-γ expression decreases in ob/ob mice [ 193 ] and other studies have reported lower adiponectin values in the adipose tissue and in the spleen [ 193 , 195 ].…”

“…Moreover, LPS levels are higher in plasma from ob/ob mice [ 198 ] and in C57BL/6NTac mice on HFD [ 174 ]. Additionally, NF-kB levels are elevated in the brain of ob/ob mice [ 196 ]. Other markers, such as CD11 and CD86 are increased in the brain and visceral fat tissue, whereas the expression of CD206 decreases [ 196 , 197 ].…”

“…Additionally, NF-kB levels are elevated in the brain of ob/ob mice [ 196 ]. Other markers, such as CD11 and CD86 are increased in the brain and visceral fat tissue, whereas the expression of CD206 decreases [ 196 , 197 ]. In line with these observations, oxidative stress is also severely affected in ob/ob animals and increased protein oxidation and lipoperoxidation are observed, accompanied by lower activity of antioxidant enzymes in kidney and heart [ 195 ].…”