In vitro effects of sitosterol and sitostanol on mitochondrial respiration in human brown adipocytes, myotubes and hepatocytes

Abstract

Purpose Lowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabolism. We here hypothesize that high levels of plant sterols and stanols stimulate whole-body energy expenditure, which can be attributed to changes in mitochondrial function of brown adipose tissue (BAT), skeletal muscle and liver. Methods Phytosterolemic mice were fed chow diets for 32 weeks to examine whole-body weight gain. In vitro, 24-h incubation were performed in adipocytes derived from human BAT, human myotubes or HepG2 human hepatocytes using sitosterol or sitostanol. Following mitochondrial function was assessed using seahorse bioanalyzer. Results Chow feeding in phytosterolemic mice resulted in diminished increase in body weight compared to control mice. In vitro, sitosterol or sitostanol did not change mitochondrial function in adipocytes derived from human BAT or in cultured human myotubes. Interestingly, maximal mitochondrial function in HepG2 human hepatocytes was decreased following sitosterol or sitostanol incubation, however, only when mitochondrial function was assessed in low glucose-containing medium. Conclusions Beneficial in vivo effects of plant sterols and stanols on lipid and lipoprotein metabolism are well recognized. Our results indicate that alterations in human mitochondrial function are apparently not involved to explain these beneficial effects.

Phytosterol organic acid esters: Characterization, anti-inflammatory properties and a delivery strategy to improve mitochondrial function

“…7 A–D). Similar to previous studies, we did not find direct effects or sufficiently significant differences (p < 0.05) of phytosterols on mitochondrial function under stress in normal cell culture conditions ( Nascimento et al, 2020 ). Although phytosterols are considered to be resistant to oxidative stress and lipid peroxidation via estrogen receptor mediated PI3K/GSK3 signaling ( Shi et al, 2013 ), and increasing mitochondrial membrane potential under stress conditions ( Wong et al, 2016 ).…”

“…Although phytosterols are considered to be resistant to oxidative stress and lipid peroxidation via estrogen receptor mediated PI3K/GSK3 signaling ( Shi et al, 2013 ), and increasing mitochondrial membrane potential under stress conditions ( Wong et al, 2016 ). Interestingly, previous studies highly recommend that phytosterols have a better effect to the mitochondrial function in low glucose-containing medium ( Nascimento et al, 2020 ). Notably, protocatechuic acid ( Abdelmageed et al, 2021 ), sinapic acid ( Cherng et al, 2013 ), and vanillic acid ( Chang et al, 2015 ) are associated with hypoglycemia, which is considered one reason for the improvement of mitochondrial functional regulation by stigmasteryl phenolates.…”

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

“…Of note, although only a few data are currently available, many investigations have suggested that mitochondria and oxidative stress constitute potential direct or indirect targets of phytosterols. In this context, sitostanol and sitosterol show beneficial effects on mitochondrial respiration in human hepatocytes, brown adipocytes, and myotubes [ 94 ]. Moreover, sitosterol has been shown to enhance mitochondrial ATP content and membrane potential in H9c2 cardiomyocytes [ 95 ].…”

Study on the mechanism of Baihe Dihuang decoction in treating menopausal syndrome based on network pharmacology

“…The oxidation products of stigmasterol interfere with the female sex hormone 17β-estradiol in human breast and endometrial cells. [ 47 ] Stigmasterol Causes Ovarian Cancer Cell Apoptosis by Inducing Endoplasmic Reticulum and Mitochondrial Dysfunction. [ 48 ] Stigmasterol is also a potential metabolic regulator of neurodegenerative diseases.…”