Silibinin attenuates adipose tissue inflammation and reverses obesity and its complications in diet-induced obesity model in mice

Mohammad Alsaggar,Tamam El-Elimat,Karem H Alzoubi,Qutaibah Ababneh,Nidal Qinna,Shifa Bdour

doi:10.1186/s40360-020-0385-8

Mohammad Alsaggar, Tamam El-Elimat + Show 4 more

Open Access

https://doi.org/10.1186/s40360-020-0385-8

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Abstract

BackgroundObesity is a multifactorial chronic disease that comprises several pathological events, such as adipose hypertrophy, fatty liver and insulin resistance. Inflammation is a key contributer to development of these events, and therefore, targeting inflammation is increasingly considered for management of obesity and its complications. The aim of the current study was to investigate therapeutic outcomes of anti-inflammatory activities of the natural compound Silibinin in reversing obesity and its complication in mice.MethodsC57BL/6 male mice were fed high-fat diet for 8 weeks until development of obesity, and then injected with 50 mg/kg silibinin intraperitoneally twice per week, or vehicle for 8 weeks. Throughout the experiment, mice were continuously checked for body weight and food intake, and glucose tolerance test was performed toward the end of the experiment. Animals were sacrificed and serum and tissues were collected for biochemical, histological, and gene expression analysis to assess silibinin effects on adipose inflammation, fat accumulation, liver adipogenesis and glucose homeostasis.ResultsSilibinin treatment reversed adipose tissue inflammation and adipocyte hypertrophy, and blocked progression in weight gain and obesity development with no significant effects on rates of food intake. Silibinin also reversed fatty liver disease and restored glucose homeostasis in treated animals, and reversed hyperglycemia, hyperinsulinemia and hypertriglyceridemia.ConclusionIn this study, we demonstrated that silibinin as an anti-inflammatory therapy is a potential alternative to manage obesity, as well as its related complications. Moreover, silibinin-based therapies could further evolve as a novel treatment to manage various inflammation-driven disorders.

Highlights

Obesity is a multifactorial chronic disease that comprises several pathological events, such as adipose hypertrophy, fatty liver and insulin resistance
Silibinin treatment suppressed and reversed diet–induced weight gain without affecting food intake Given the anti-inflammatory properties of silibinin, we first investigated the beneficial outcomes of silibinin treatment on progression of HFD-induced obesity in mice
Both treated and control groups started the experiment at comparable body weight of around 37 g; at the end of experiment the treated animals lost around 2 g to end up with roughly 35 g, while control animals progressed in weight gain to reach more than 42 g

Summary

Introduction

Obesity is a multifactorial chronic disease that comprises several pathological events, such as adipose hypertrophy, fatty liver and insulin resistance. Accumulated fat in adipose tissue induces oxidative and metabolic stress within adipocytes, and triggers increased expression of pro-inflammatory cytokines, including TNF-α and IL-1 These cytokines lead to the recruitment of immune cells, macrophages to aid in tissue remodeling, which in turn promotes increased production of reactive oxygen species (ROS) and eventually resulting in oxidative stress (OS), both locally and systemically [6]. More research is currently directed to investigate inflammation’s roles in obesity pathogenesis, and to explore and develop strategies to tackle inflammation for management of obesity and its related diseases. This approach has been proven effective in various studies in animal models of obesity [8]

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