The Anti‐adipogenic Effects of Neohesperidin Dihydrochalcone Derivatives on Human Adipose‐Derived Stem Cells

Obesity, described by an excess accumulation of adipocyte, has emerged as one of the major public health problems. Excess adipocyte increases the risk for multiple pathological conditions and metabolic disorders such as dyslipidemia, hypertension and cancer. Oxygen free radicals are highly reactive and generated by incomplete reduction of oxygen molecule during oxidative phosphorylation which is expected to cause damage to various cellular functions. Mitochondrial electron transport chain is thought to be as a major intracellular generator of reactive oxygen species (ROS). Adipose‐derived stem cells (ADSCs) are generally extracted from adipose tissue and have the ability to differentiate into multiple mesodermal cell types, such as adipocytes, osteoblasts, chondrocytes and neuronal cells. ROS positively stimulate adipogenic differentiation, it is significant to degrade the level of ROS for the preventing above diseases. Nuclear factor erythroid 2‐related factor‐2 (Nrf2), a transcription factor defined as one of the key antioxidant regulators. In the cytoplasm, under normal conditions, Nrf2 is constructively bound to Kelch‐like ECH associating protein 1 (Keap 1) protein. But exposuring to ROS, Nrf2 is dissociated from the Keap‐Nrf2 complex and translocated from the cytoplasm to the nucleus. Subsequently, Nrf2 promotes expression of antioxidant enzyme genes such as heme oxygenase 1 (HO‐1) and NAD(P)H:Quinone Oxidoreductase 1 (NQO‐1) by binding to the antioxidant response element (ARE). Neohesperidin is a flavonoid compounds originated from peel of citrus fruits and its hydrogenated form, Neohesperidin dihydrochalcone (NHDC) has antioxidant activity. Thus, we observed the anti‐adipogenic effects of NHDC derivatives on human adipose‐derived stem cells (hADSC) through Nrf2 activation. Cell viability and compounds' proper concentrations were set by MTS assay. The effect of these compounds on suppressing oxidative stress, lipid accumulation, and adipogenic differentiation from hADSCs was investigated using Oil Red O staining, reverse‐transcriptase polymerase chain reaction (RT‐PCR), quantitative real‐time PCR (qPCR), and western blotting. And also intracellular ROS production was measured using 2′, 7′‐dichlorofluorescin diacetate (DCF‐DA). It was first found that NHDC derivatives treatment during adipogenic differentiation of hADSCs reduced lipid droplets accumulation and increased expression level of anti‐oxidant marker (Nrf2, HO‐1, NQO‐1). But expression of adipogenic markers, peroxisome proliferator‐activated receptor gamma (PPAR γ) and CCAAT/enhancer‐binding protein α (C/EBP α) were downregulated. The results demonstrate that NHDC derivatives play an efficacious role in inhibiting adipogenic differentiation of hADSCs through reducing cellular oxidative stress. Therefore, using these compounds as therapeutic applications including development of functional foods and pharmaceutical agents is worthy of note for health promoting. Support or Funding Information This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science, ICT & Future Planning (NRF‐2015R1C1A1A01053726) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .