Signaling Targets Related to Antiobesity Effects of Capsaicin: A Scoping Review

Abstract

The search for new antiobesogenic agents is increasing because of the current obesity pandemic. Capsaicin (Caps), an exogenous agonist of the vanilloid receptor of transient potential type 1 (TRPV1), has shown promising results in the treatment of obesity. This scoping review aims to verify the pathways mediating the effects of Caps in obesity and the different methods adopted to identify these pathways. The search was carried out using data from the EMBASE, MEDLINE (PubMed), Web of Science, and SCOPUS databases. Studies considered eligible evaluated the mechanisms of action of Caps in obesity models or cell types involved in obesity. Nine studies were included and 100% (n = 6) of the in vivo studies showed a high risk of bias. Of the 9 studies, 66.6% (n = 6) administered Caps orally in the diet and 55.5% (n = 5) used a concentration of Caps of 0.01% in the diet. In vitro, the most tested concentration was 1 μM (88.9%; n = 8). Capsazepine was the antagonist chosen by 66.6% (n = 6) of the studies. Seven studies (77.8%) linked the antiobesogenic effects of Caps to TRPV1 activation and 3 (33.3%) indicated peroxisome proliferator-activated receptor (PPAR) involvement as an upstream connection to TRPV1, rather than a direct metabolic target of Caps. The main secondary effects of Caps were lower weight gain (33.3%; n = 3) or loss (22.2%; n = 2), greater improvement in lipid profile (33.3%; n = 3), lower white adipocyte adipogenesis (33.3%; n = 3), browning process activation (44.4%; n = 4), and higher brown adipocyte activity (33.3%; n = 3) compared with those of the control treatment. Some studies have shown that PPAR agonists modulate TRPV1 activity, and no study has evaluated the simultaneous antagonism of these 2 receptors. Consequently, further studies are necessary to elucidate the role of each of these signaling molecules in the antiobesogenic effects of Caps.

Keywords: PPARγ; TRPV1; adipogenesis; browning; capsaicin; obesity; thermogenesis.

FIGURE 1

Overview of the flowchart of the selection of included studies.

FIGURE 2

Bias risk assessment of studies included in the scoping review by the RoB tool for animal intervention studies: SYRCLE's RoB tool. RoB, risk-of-bias; SYRCLE, SYstematic Review Centre for Laboratory animal Experimentation.

FIGURE 3

Capsaicin pathways of action found in the studies reviewed from experiments conducted in vivo and in vitro. The studies included in this scoping review were divided into 3 main outcomes: TRPV1-dependent, TRPV1-independent, and PPARγ. PPARγ, peroxisome proliferator-activated receptor γ; TRPV1, transient receptor potential vanilloid 1.

FIGURE 4

Main secondary capsaicin effects found in vivo and in vitro in the included studies. The in vivo findings were divided by tissue or organ in which they were analyzed. All in vitro findings were grouped in a single box.