Flazin as a Lipid Droplet Regulator against Lipid Disorders

Abstract

Lipid disorders are closely related to numerous metabolic diseases, and lipid droplets (LDs) have been considered as a new target for regulating lipid metabolism. Dietary intervention and nutraceuticals provide safe and long-term beneficial effects for treating metabolic diseases. Flazin is a diet-derived bioactive constituent mainly existing in fermented foods, of which the lipid metabolism improvement function has not been studied. In this study, the effect of flazin on lipid regulation at both cell level and organelle level was investigated. Lipidomic profiling showed that flazin significantly decreased cellular triglyceride (TG) by 12.0–22.4% compared with modeling groups and improved the TG and free fatty acid profile. LD staining revealed that flazin efficiently reduced both cellular neutral lipid content by 17.4–53.9% and LD size by 10.0–35.3%. Furthermore, nanoelectrospray ionization mass spectrometry analysis proved that flazin exhibited a preferential suppression of LD TG and regulated LD morphology, including a size decrease and surface property improvement. An evaluation of related gene expression suggested the mechanism to be lipolysis promotion and lipogenesis inhibition. These findings indicated that flazin might be an LD regulator for reversing lipid metabolism disturbance. Moreover, the strategy proposed in this study may contribute to developing other nutraceuticals for treating lipid disorder-related metabolic diseases.

Inhibitors of Asexual Reproduction of the Plant Pathogen Phytophthora from Tomato Juice: Structure–Activity Relationships and Transcriptome Analysis

“…Flazin was originally isolated as a fluorescent substance from Japanese rice wine lees in 1936, and the structure was determined in 1986. , Flazin was also isolated from tomato juice . Although its biological effects have recently been studied, − no studies have examined the inhibition of microbial sporogenesis. Naringenin is a flavanone that is widely distributed in nature, especially in fruits and vegetables, and many biological effects of naringenin have been reported.…”

Oxidative Stress and Lipid Dysregulation in Lipid Droplets: A Connection to Chronic Kidney Disease Revealed in Human Kidney Cells

“…The treatment of FA to cells has profoundly affected the LD TG profile in our previous reports [ 24 , 27 ]. Currently, the results of FA18:1, FA18:2, and FA18:3 that were supplemented to HK-2 cells supported this viewpoint, as they were supposed to be taken up directly by the cells and be esterized as LD TG, while FA16:0, FA20:4, FA20:5, and FA22:6 showed no such function.…”

“…The PC/TG ratio exhibited a decreasing trend with the extended oxidation time, reaching 59.6 to 17.9% of the control (0 h) from 0.5 h to 4 h. The PC forms the cylindrical structures in the biological membranes, while the PE form the conical structures [ 38 ]. Therefore, a decreased PC/PE ratio is considered to promote packing defects and thereby favor the localization of perilipin to the LD surface, which contributes to lipid accumulation and LD growth [ 27 ]. According to the present results, the supplemented oxHDL decreased the PC/PE ratio, which suggested that it would aggravate the effect on the packing defects and result in LD enlargement.…”

“…Oil red O dye (Wako Pure Chemical Industries), which is used for LD staining, was dissolved in isopropanol to prepare the stock solution (3 mg/mL). The working solution was prepared according to our previous study [ 27 ]; in brief, the stock solution (15 mL) was diluted with 10 mL of distilled water, and the final concentration was 1.8 mg/mL. The newly prepared working solution was thereafter filtrated using a 0.45 μm filter (Merck Millipore Ltd., Burlington, MA, USA) before use.…”

“…The LD sampling was conducted using an IM-11 three-dimensional mobile manipulator (Narishige Group), coupled with an IX71 inverted microscope in a bright field, as in our previous studies [ 24 , 27 ]. The culture medium of the cells was washed and then replaced with 0.6 mL 160 mM ammonium formate solution, and the LDs were aspirated into nanotips using the microinjector.…”