Raspberry ketone, a naturally occurring phenolic compound, inhibits adipogenic and lipogenic gene expression in 3T3-L1 adipocytes

Abstract

Context: Raspberry ketone (RK) is a natural phenolic compound of red raspberry. The dietary intake of RK has been reported to exert anti-obese actions and alter the lipid metabolism in vivo and human studies. Objective: To elucidate a possible mechanism for anti-obese actions of RK, the effects of RK on the adipogenic and lipogenic gene expression in 3T3-L1 adipocytes were investigated. Materials and methods: 3T3-L1 maturing pre-adipocytes were treated from day 2 to day 8 of differentiation and mature adipocytes for 24 h on day 12 with 1, 10, 20, and 50 mM of RK. Triacylglycerols were assessed by spectrophotometry and gene expression by quantitative realtime polymerase chain reaction (qRT-PCR). Results: Treatment of adipocytes with RK suppressed adipocyte differentiation and fat accumulation in a concentration-dependent manner. RK suppressed the expression of major genes involved in the adipogenesis pathway including peroxisome proliferator-activated receptor-g (PPARg) and CCAAT enhancer binding protein-a (C/EBPa), which led to further down-regulation of adipocyte fatty acid-binding protein-2 (aP2). In addition, treatment with 10 mM of RK also reduced mRNA levels of lipogenic genes such as acetyl-CoA carboxylase-1 (ACC1), fatty acid synthase (FASN), and stearoyl-CoA desaturase-1 (SCD1). In mature adipocytes, RK increased the transcriptional activities of genes involved in lipolysis and the oxidative pathways including adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), and carnitine palmitoyl transferase-1B (CPT1B). Discussion and conclusion: These findings suggest that RK holds great promise for an herbal medicine with the biological activities altering the lipid metabolism in 3T3-L1 adipocytes.

Development of obesity is reduced in high-fat fed mice fed whole raspberries, raspberry juice concentrate, and a combination of the raspberry phytochemicals ellagic acid and raspberry ketone

“…Although RK is promoted as a dietary supplement, as a product to help promote or maintain weight loss, there are few studies that document a clear effect [32,33]. More recently, publications investigating aspects of raspberry ketone have evaluated bone cell differentiation [34]; fatty liver [35]; and gene expression changes [36]. The efficacy of RK is not known with certainty at this time.…”

Ellagic Acid and Urolithins A and B Differentially Regulate Fat Accumulation and Inflammation in 3T3-L1 Adipocytes While Not Affecting Adipogenesis and Insulin Sensitivity

“…This suggests that the insulin sensitization induced by PPARγ is in part mediated by c/EBPα activation. On the other hand, in addition to controlling insulin action, c/EBPα is required for maintaining expression of PPARγ in the mature fat cell [27], and both are considered key regulators in fatty acid biosynthesis and accumulation [28]. On the basis of the intracellular triglyceride accumulation results, we were expecting a decrease in c/EBPα and PPARγ protein expression after the treatments with ellagic acid and urolithin A.…”

Raspberry ketone ingestion in dogs

“…Experimental studies have shown that it alters lipid metabolism in adipocytes (Park 2015) and enhances noradrenaline-induced lipolysis (Morimoto and others 2005). There is limited information on the safety and toxicity of raspberry ketone in both animals and humans (Bredsdorff and others 2015).…”