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

Myeongjoo Son,Junwon Choi,Ji Tae Jang,Kuk Hui Son,Kook Yang Park,Chang Hu Choi,Kyunghee Byun,Seyeon Oh

doi:10.3390/nu11112773

Myeongjoo Son, Junwon Choi + Show 6 more

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https://doi.org/10.3390/nu11112773

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Journal: Nutrients	Publication Date: Nov 14, 2019
Citations: 15	License type: CC BY 4.0

Affiliation: Gachon University, Gachon University Gil Medical Center

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.

Highlights

Leptin, the most well-known adipokine derived from adipocytes, regulates food intake and energy expenditure by binding to the long isoform of leptin receptor (Ob-R) in the central nervous system (CNS), mainly in the hypothalamic nuclei; it plays a crucial role in the maintenance of body weight [1,2]
MRNA levels of (F) PPARγ, (G) ACC, and (H) FAS in palmitic acid–conjugated bovine serum albumin (PA-BSA) (0.25 mM) treated 3T3L-1 cells were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)
Adipocytes secrete pro-inflammatory cytokines [10,11], which is in line with our results that tumor necrosis factor α (TNF-α) and IL-6 expression in adipose tissue was increased by high-fat diet (HFD) but decreased by PPB

Summary

Introduction

The most well-known adipokine derived from adipocytes, regulates food intake and energy expenditure by binding to the long isoform of leptin receptor (Ob-R) in the central nervous system (CNS), mainly in the hypothalamic nuclei; it plays a crucial role in the maintenance of body weight [1,2]. In genetically-induced obese mice (ob/ob) which cannot synthesize leptin, treatment with recombinant leptin is highly effective at decreasing appetite and reversing obesity [3,4]. In diet-induced obese (DIO) mice or obese humans, leptin fails to prevent weight gain, even at Nutrients 2019, 11, 2773; doi:10.3390/nu11112773 www.mdpi.com/journal/nutrients. Nutrients 2019, 11, 2773 high serum levels. Such unresponsiveness to endogenous or exogenous leptin is referred to as ‘leptin resistance’ [4,5]. Molecular leptin sensitivity, defined as the ability of leptin to phosphorylate and thereby activate STAT3 [3,6], is reduced after high-fat diet (HFD) intake [7].

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