Theophylline Extracted from Fu Brick Tea Affects the Metabolism of Preadipocytes and Body Fat in Mice as a Pancreatic Lipase Inhibitor.

Tian-Tian Liu,Gui-Li Huang,Long Liu,Qing-Xi Chen,Qin Wang,Xiao-Tian Liu

doi:10.3390/ijms23052525

Abstract

The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers’ attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC50 of 1.02~0.03 μg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.

Highlights

Adipose tissue is the central organ that maintains homeostasis, and white adipose tissue (WAT) is an important part of the body that stores fat and regulates energy metabolism, but the excessive accumulation of WAT leads to the development of obesity [1]
We found that Fu Brick Theophylline (FBT) can significantly inhibit the proliferation of preadipocytes, but lactic dehydrogenase (LDH) treatment experiments confirmed that FBT is not toxic to cells
We found that FBT treatment lowered hepatic fat accumulation and improved glucose homeostasis in high-fat diet (HFD)-fed mice

Summary

Introduction

Adipose tissue is the central organ that maintains homeostasis, and white adipose tissue (WAT) is an important part of the body that stores fat and regulates energy metabolism, but the excessive accumulation of WAT leads to the development of obesity [1]. Many studies have shown that the secretion and expression of various inflammatory factors increase in the white fat of type 2 diabetes patients. These inflammatory factors and inflammatory markers can cause insulin resistance by interfering with normal insulin signal transduction pathways. Lipase plays a key role in human fat metabolism. It breaks down the oil in food into small molecules of glycerol and fatty acids that the body can absorb and metabolize [4]. In previous studies of pancreatic lipase inhibitors, most inhibitors have shown an effect of improving fatty liver damage and reducing blood lipid levels in the body [6]

Methods

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Discussion

Conclusion