Oxygenated Water Inhibits Adipogenesis and Attenuates Hepatic Steatosis in High-Fat Diet-Induced Obese Mice

Yuh-Jen Cheng,Chiao-Wan Hsiao,Cheng-Wei Chuang,Ching-Ping Yang,Chao-Chi Liu,Hsueh-Te Lee,Jen-Ning Tsai,Yih-Hsin Chang,Fang-Yeh Chu,Ming-Yuh Shiau

doi:10.3390/ijms21155493

Abstract

The expansion of adipose tissue mass is the primary characteristic of the process of becoming obesity, which causes chronic adipose inflammation and is closely associated with type 2 diabetes mellitus (T2DM). Adipocyte hypertrophy restricts oxygen availability, leading to microenvironmental hypoxia and adipose dysfunction. This study aimed at investigating the effects of oxygenated water (OW) on adipocyte differentiation (adipogenesis) and the metabolic function of mature adipocytes. The effects of OW on adipogenesis and the metabolic function of mature adipocytes were examined. Meanwhile, the in vivo metabolic effects of long-term OW consumption on diet-induced obesity (DIO) mice were investigated. OW inhibited adipogenesis and lipid accumulation through down-regulating critical adipogenic transcription factors and lipogenic enzymes. While body weight, blood and adipose parameters were not significantly improved by long-term OW consumption, transient circulatory triglyceride-lowering and glucose tolerance-improving effects were identified. Notably, hepatic lipid contents were significantly reduced, indicating that the DIO-induced hepatic steatosis was attenuated, despite no improvements in fibrosis and lipid contents in adipose tissue being observed in the OW-drinking DIO mice. The study provides evidence regarding OW’s effects on adipogenesis and mature adipocytes, and the corresponding molecular mechanisms. OW exhibits transient triglyceride-lowering and glucose tolerance-improving activity as well as hepatic steatosis-attenuating functions.

Highlights

Studies regarding oxygen concentration and diseases are emerging, such as the effects of oxygen contents and hypoxia on physiological functions and tissue damage
Abundant evidence shows that the rapid expansion of the major energy reservoir, adipose tissues, in obese individuals leads to a shortage of oxygen supply, which successively results in insulin resistance and type 2 diabetes mellitus (T2DM) [1]
Primary antibodies against β-Actin, AKT, phosphyorylated AKT, GAPDH, glycogen synthase kinase-3 beta (GSK-3β), phosphorylated GSK-3β Ser-9, Hypoxia-inducible factors (HIFs)-1α, NF-κB p65, NF-κB p50, PAI-1 and phosphoenolpyruvate carboxykinase (PEPCK) were purchased from Abcam (Cambridge, UK); those against fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), pJNK and peroxisome proliferator-activated receptor gamma (PPARγ) were purchased from Cell Signaling (Danvers, MA, USA); those against JNK, c-Jun, sterol regulatory element-binding protein (SERBP1) and vascular endothelial growth factor A (VEGFA) were purchased from Santa Crutz; and that against diglyceride acyltransferase 2 (DGAT2) was purchased from Genetex

Summary

Introduction

Studies regarding oxygen concentration and diseases are emerging, such as the effects of oxygen contents and hypoxia on physiological functions and tissue damage. Abundant evidence shows that the rapid expansion of the major energy reservoir, adipose tissues, in obese individuals leads to a shortage of oxygen supply, which successively results in insulin resistance and type 2 diabetes mellitus (T2DM) [1]. As for in vivo studies, the epididymal adipose tissue of obese mice has lower oxygen pressure than that of mice with normal body weight [4]. White adipose tissues in leptin-deficient mice have a hypoxic status [1]. These reports reveal that obesity leads to adipose tissue hypoxia and contributes to adipose dysfunction

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