2 research outputs found
Multidrug and Toxic Compound Extrusion Protein‑1 (MATE1/SLC47A1) Is a Novel Flavonoid Transporter
Dietary
flavonoids have various biological functions. However,
their cellular transport mechanisms are largely unknown. We have determined
that the multidrug and toxic compound extrusion transporter-1 (MATE1)
is a membrane transporter for flavonoids and has a high affinity for
quercetin. HEK293T cells overexpressing MATE1 exhibited increased
intracellular quercetin accumulation. This effect disappeared in the
presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2
cells expressed MATE1 significantly, with the uptake quercetin of
which was dramatically reduced with MATE1 inhibition. On the basis
of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes
and the endoplasmic reticulum (ER) as well as in plasma membranes
in the liver and intestine, which suggests potential accumulation
of quercetin in peroxisomes and the ER in these tissues. Fluorescent
microscopic analysis confirmed selective accumulation of qurcetin
in peroxisome. The effects of quercetin on cellular lipid reduction
and glucose uptake were exaggerated with MATE1 overexpression. In
conclusion, MATE1 is a membrane transporter for quercetin; its overexpression
enhances the hypolipidemic activity of quercetin and cellular glucose
transport. Considering the low bioavailability of quercetin, appropriate
regulation of MATE1 expression may optimize cellular quercetin concentrations
and promote health benefits
Critical Role of Peroxisome Proliferator Activated Receptor-δ on Body Fat Reduction in C57BL/6J and Human Apolipoprotein E2 Transgenic Mice Fed Delipidated Soybean
The consumption of soy protein and fiber reduces body fat accumulation; however, the mechanism of this effect has not been clearly understood. We investigated the antiobesogenic effect of soy protein and fiber in two different mouse models. Normolipidemic nonobese C57BL/6J and hyperlipidemic obese human apolipoprotein E2 transgenic mice were fed either delipidated soybean (DLSB) containing soy protein and fiber or a control diet. The DLSB-fed mice showed a significant reduction in body weight gain and adiposity compared with controls, in both C57BL/6J and apoE2 mice. All metabolic parameters were significantly improved in the DLSB group compared with controls: total cholesterol, low-density lipoprotein cholesterol, insulin, and leptin levels were significantly reduced. Adiponectin concentrations were significantly elevated, and glucose tolerance was improved. In both types of DLSB-fed mice, the specific induction of PPAR-δ protein expression was evident in muscle and adipose tissues. The expression of PPAR-δ target genes in the DLSB-fed mice was also significantly altered. Acetyl-CoA carboxylase-1 and fatty acid synthase levels in adipose tissue were downregulated, and uncoupling protein-2 in muscle was upregulated. Intestinal expression of fatty acid transport protein-4, cluster of differentiation-36, and acyl-CoA synthetase were significantly downregulated. We propose that marked activation of PPAR-δ is the primary mechanism mediating the antiobesogenic effect of soybean and that PPAR-δ has multiple actions: induction of thermogenesis in muscle, reduction of fatty acid synthesis in adipose tissue, and reduction of fatty acid uptake in intestinal tissue