Novel anti-obesity effects of beer hops compound xanthohumol: role of AMPK signaling pathway

Abstract

BackgroundObesity alters adipose tissue metabolic and endocrine functioning, leading to an increased adiposity and release of pro-inflammatory cytokines. Various phytochemicals have been reported to contribute to the beiging of white adipose tissue in order to ameliorate obesity by increasing thermogenesis. Here, we show that the prenylated chalcone, xanthohumol (XN), induces beiging of white adipocytes, stimulates lipolysis, and inhibits adipogenesis of murine 3T3-L1 adipocytes and primary human subcutaneous preadipocytes and these effects are partly mediated by the activation of the AMP-activated protein kinase (AMPK) signaling pathway.Methods3T3-L1 adipocytes and primary human subcutaneous preadipocytes were differentiated using a standard protocol and were treated with various concentrations of XN, dorsomorphin, an AMPK inhibitor, or AICAR, an AMPK activator, to investigate the effects on adipogenesis, beiging and lipolysis.ResultsXN induced beiging of white adipocytes as witnessed by the increased expression of beige markers CIDE-A and TBX-1. XN increased mitochondrial biogenesis, as evidenced by increased mitochondrial content, enhanced expression of PGC-1α, and the thermogenic protein UCP1. Following 24 h of treatment, XN also increased oxygen consumption rate. XN stimulated lipolysis of mature 3T3-L1 and primary human subcutaneous adipocytes and inhibited adipogenesis of maturing adipocytes. XN activated AMPK and in turn, XN-induced upregulation of UCP1, p-ACC, HSL, and ATGL was downregulated in the presence of dorsomorphin. Likewise, an XN-induced decrease in adipogenesis was reversed in the presence of dorsomorphin.ConclusionsTaken together, XN demonstrates anti-obesity effects by not only inducing beiging but also decreasing adipogenesis and inducing lipolysis. The anti-obesity effects of XN are partly mediated by AMPK signaling pathway suggesting that XN may have potential therapeutic implications for obesity.Electronic supplementary materialThe online version of this article (10.1186/s12986-018-0277-8) contains supplementary material, which is available to authorized users.

Phenols and Melanoidins as Natural Antioxidants in Beer. Structure, Reactivity and Antioxidant Activity

“…More specifically, some antioxidants have been studied such as xanthohumol (flavonoid present in beer and found only in hops [30]) and its cyclization product, isoxanthohumol, which have been studied previously by us [31] both present anti-cancer properties. Xanthohumol displays many bioactive effects such as antioxidant, anti-inflammatory, anti-microbial, hypoglycemic, and anti-obesity [32,33]. In particular, this compound is effective against different types of cancer [30] among which are: breast [34], ovarian [34], prostate [35], of colon [36] and pancreas [37] as well as being effective against leukemia [38] and protecting DNA against oxidative damage [39].…”

Benefits of Xanthohumol in Hyperlipidaemia, Obesity and Type 2 Diabetes Mellitus: A Review

“…In vitro studies: In a study of adipocytes and primary human subcutaneous preadipocytes, addition of XN 6.25-25 uM demonstrated anti-obesity potential by stimulating conversion of WAT to BAT via MAPK signalling pathways as well as decreasing adipogenesis and promoting lipolysis [29]. Such findings were also confirmed in adipocytes by Yang et al, at 25-100 uM [19].…”

Lipocalin-2 deficiency may predispose to the progression of spontaneous age-related adiposity in mice

“…3T3-L1 cells at passage numbers between 6 and 15 were used and the differentiation potential of the cells was determined by the morphological changes and lipid deposition after the induction of differentiation process where preadipocytes develop into mature adipocytes. Differentiation of 3T3-L1 preadipocytes was carried out as we previously described 71,72 . Briefly, 3T3-L1 preadipocytes were cultured in medium containing Dulbecco's Modified Eagle Medium (DMEM) GlutaMAX with 10% calf serum and 1% penicillin-streptomycin.…”