Benzyl isothiocyanate ameliorates lipid accumulation in 3T3-L1 preadipocytes during adipocyte differentiation

Abstract

Benzyl isothiocyanate (BITC) is an organosulfur compound derived from cruciferous vegetables and papaya seeds. In this study, we investigated the effect of BITC on the lipid accumulation in 3T3-L1 preadipocytes during adipocyte differentiation. The treatment of BITC during the differentiation-inducing stage significantly ameliorated the lipid accumulation, whereas it had no inhibitory effect during the differentiation-maintaining stage. BITC also significantly suppressed the mRNA expression of the adipocyte-specific markers, such as CCAAT/enhancer-binding protein α (C/EBPα), C/EBPβ, C/EBPδ and peroxisome proliferator-activated receptor γ. BITC significantly inhibited the phosphorylation of extracellular signal-regulated kinase phosphorylation, whereas it enhanced that of AMP-activated protein kinase. Furthermore, BITC significantly suppressed the intracellular 2-deoxyglucose uptake as well as glucose transporter 4 expression. These results suggest that inhibition of the adipocyte differentiation and glucose uptake may mainly contribute to the inhibitory effect of BITC on the lipid accumulation in 3T3-L1 preadipocytes. Abbreviations: PPARγ: peroxisome proliferator-activated receptor γ; CEBP: CCAAT/enhancer-binding protein; GLUT4: glucose transporter 4; AMPK: AMP-activated protein kinase; ERK1/2: extracellular signal-regulated kinase 1/2; MAPK: a mitogen-activated protein kinase; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; FBS: fetal bovine serum; CS: calf serum; AITC: allyl ITC; IBMX: 3-isobutyl-1-methylxanthine; LDH: lactate dehydrogenase; KRH: Krebs-Ringer-Hepes-bicarbonate; 2-DG: 2-deoxy-d-glucose.

Genistein regulates adipogenesis by blocking the function of adenine nucleotide translocase-2 in the mitochondria

“…Genistein treatment decreased intracellular ATP levels and induced AMPK phosphorylation in ASCs. Some studies have reported that food-derived factors such as flavonoids and catechins induce AMPK activation, and food factors with an antiadipogenic effect are considered to exert their effect via AMPK activation (Liang et al 2018;Choi et al 2014). However, for some phytochemicals, it is not well known how they lead to AMPK activation.…”

“…Certain phytochemicals inhibit adipogenesis and high-fat diet-induced obesity. The molecular mechanisms underlying the anti-adipogenic effects of phytochemicals are diverse and include the induction of apoptosis and inhibition of the cell cycle via various cell signaling pathways, including WNT/β-catenin signaling, mitogen-activated protein kinase pathways, and the AMP-activated protein kinase (AMPK) pathway (Ahn et al 2010;Kwon et al 2012;Liang et al 2018). AMPK plays an important role in the maintenance of cellular energy homeostasis (Hardie 2007).…”

Benzyl Isothiocyanate Produced by Garden Cress (<i>Lepidium sativum</i>) Prevents Accumulation of Hepatic Lipids

“…Therefore, moderate levels of BITC, which reduce fatty liver and the levels of plasma TGs, may be useful for preventing such symptoms. SFN (18,24) and BITC (25) improve lipid metabolism by suppressing lipogenesis in adipose tissue via the AMP-activated protein kinase signaling pathway. Furthermore, SFN ameliorates abnormal lipid metabolism in a mitochondrial-dependent manner (26,27).…”

Functional Application of Sulfur-Containing Spice Compounds

“…AITC can also inhibit adipocyte differentiation by suppressing galectin-12 levels in 3T3L1 cells and has antiobesity effects in HFD-fed mice . In addition, BITC significantly suppresses the mRNA expression of the adipocyte-specific markers, such as C/EBPα, C/EBPβ, C/EBPδ, and PPAR-γ, and inhibits the intracellular 2-deoxyglucose (2-DG) uptake and glucose transporter 4 (GLUT4) expression, thereby inhibiting lipid accumulation in 3T3-L1 preadipocytes . Another study showed that oral administration of phenethyl isothiocyanate (PEITC) in mice significantly reduced food intake, and stimulated hypothalamic leptin signaling PEITC effectively inhibits protein tyrosine phosphatase 1B (PTP1B) by binding to the reactive cysteinyl thiol.…”

“…41 In addition, BITC significantly suppresses the mRNA expression of the adipocyte-specific markers, such as C/EBPα, C/EBPβ, C/EBPδ, and PPAR-γ, and inhibits the intracellular 2deoxyglucose (2-DG) uptake and glucose transporter 4 (GLUT4) expression, thereby inhibiting lipid accumulation in 3T3-L1 preadipocytes. 44 Another study showed that oral administration of phenethyl isothiocyanate (PEITC) in mice significantly reduced food intake, and stimulated hypothalamic leptin signaling PEITC effectively inhibits protein tyrosine phosphatase 1B (PTP1B) by binding to the reactive cysteinyl thiol. This activates the production of leptin (a weight loss hormone), which through the hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway reduces food intake.…”