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

Nutrients. 2019 Nov 14;11(11):2773. doi: 10.3390/nu11112773.

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.

Keywords: Ecklonia cava; leptin resistance; obese; phlorotannins; pyrogallol-phloroglucinol-6,6-bieckol.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Brain / drug effects*
  • Diet / adverse effects
  • Disease Models, Animal
  • Eating / drug effects
  • Endoplasmic Reticulum Stress
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Leptin / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • NF-kappa B
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Phaeophyceae / chemistry*
  • Phloroglucinol / pharmacology
  • Phloroglucinol / therapeutic use*
  • Pyrogallol / pharmacology
  • Pyrogallol / therapeutic use*
  • RAW 264.7 Cells
  • STAT3 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • Toll-Like Receptor 4
  • Weight Gain / drug effects

Substances

  • Leptin
  • NF-kappa B
  • STAT3 Transcription Factor
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Pyrogallol
  • Phloroglucinol