Puerarin Attenuates Obesity-Induced Inflammation and Dyslipidemia by Regulating Macrophages and TNF-Alpha in Obese Mice.

Ji-Won Noh,Min-Soo Jun,Hee-Kwon Yang,Byung-Cheol Lee

doi:10.3390/biomedicines10010175

Abstract

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue.

Highlights

Obesity and dietary excess are associated with hypertrophied adipocytes and high lipolysis, which results in subsequent metabolic disorders such as dyslipidemia, type 2 diabetes, cerebrovascular disease, and cancers
We identified the top 29 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis (Figure 1e), which were associated with insulin resistance and inflammation, such as TNF signaling, PI3K-Akt signaling, MAPK signaling, HIF-1 signaling, estrogen signaling, cAMP signaling, and mTOR signaling pathways
We found that the obesity-related target genes of puerarin were commonly associated with macrophages in inflammation and metabolic dysfunction in glucose and lipids

Summary

Introduction

Obesity and dietary excess are associated with hypertrophied adipocytes and high lipolysis, which results in subsequent metabolic disorders such as dyslipidemia, type 2 diabetes, cerebrovascular disease, and cancers. The major link between obesity and its complications is the chronic inflammatory response, which begins with high infiltration of adipose tissue macrophages (ATMs). Adipose tissue inflammation is characterized by a disproportion between pro-and anti-inflammatory immune cell homeostasis, in ATMs [1]. Pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and chemoattractants from adipocytes and ATMs, mediate obesity-induced insulin resistance and liver steatosis. This inflammatory cascade from adipose tissue throughout the body results in obesity-induced complications. The aim of new obesity treatment is to reduce weight and improve obesity-induced inflammation

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