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. 2020 Aug;59(5):2039-2045.
doi: 10.1007/s00394-019-02052-y. Epub 2019 Jul 17.

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

Emmani B M Nascimento  1 , Maurice Konings  1 , Gert Schaart  1 , Albert K Groen  2   3 , Dieter Lütjohann  4 , Wouter D van Marken Lichtenbelt  1 , Patrick Schrauwen  1 , Jogchum Plat  5
Affiliations

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

Emmani B M Nascimento et al. Eur J Nutr. 2020 Aug.

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.

Keywords: Brown adipose tissue; Cellular respiration; Mitochondria; Sitostanol; Sitosterol.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
High levels of plant sterol and stanol affect body weight in mice. ApoE KO or apoE × ABCG8 KO were fed a chow diet for 32 weeks. Data are expressed as mean ± SEM (n = 7). *p < 0.05
Fig. 2
Fig. 2
Sitosterol or sitostanol does not alter cellular respiration in cultured human adipocytes. Cellular respiration was measured in cultured adipocytes derived from human WAT (a) or BAT (b). Adipocytes were incubated for 24 h with sitosterol, sitostanol or vehicle only (EtOH). Cells were exposed to oligomycin (OG), norepinephrine (NE), FCCP and antimycin A + rotenone (AR) at the indicated arrows. Data are expressed as mean ± SEM (n = 7 for WAT, n = 4 for BAT)
Fig. 3
Fig. 3
Sitosterol or sitostanol does not change cellular respiration in cultured human hepatocytes (hepG2). Cellular respiration was measured in hepG2 cells in low glucose (5.5 mM, a) or high glucose (25 mM, b). Cells were incubated with oligomycin (OG), FCCP or antimycin A + rotenone (AR). Data are expressed as mean ± SD (n = 8). *p < 0.05 for sitosterol versus control, $p < 0.05 for sitostanol versus control
Fig. 4
Fig. 4
Sitosterol or sitostanol does not alter cellular respiration in cultured human myotubes. Myotubes were exposed to oligomycin (OG), FCCP, pyruvate and antimycin A + rotenone (AR). Data are expressed as mean ± SEM (n = 3)
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