Vanillic acid attenuates obesityviaactivation of the AMPK pathway and thermogenic factorsin vivoandin vitro

Abstract

Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro. High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice. Furthermore, VA inhibited lipid accumulation and reduced hepatotoxic/inflammatory markers in liver tissues of mice and HepG2 hepatocytes. VA treatment also decreased differentiation of 3T3-L1 adipocytes by regulating adipogenic factors including PPARγ and C/EBPα. AMPKα small interfering RNA was used to examine whether AMPK was associated with the actions of VA. In AMPKα-nulled 3T3-L1 cells, the inhibitory action of VA on PPARγ and C/EBPα was attenuated. Furthermore, in brown adipose tissues of mice and primary cultured brown adipocytes, VA increased mitochondria- and thermogenesis-related factors such as uncoupling protein 1 and PPARγ-coactivator 1-α. Taken together, our results suggest that VA has potential as an AMPKα- and thermogenesis-activating antiobesity agent.-Jung, Y., Park, J., Kim, H.-L., Sim, J.-E., Youn, D.-H., Kang, J., Lim, S., Jeong, M.-Y., Yang, W. M., Lee, S.-G., Ahn, K. S., Um, J.-Y. Vanillic acid attenuates obesity via activation of the AMPK pathway and thermogenic factors in vivo and in vitro.

IMPACT OF PHENOLIC ACIDS ON THE ENERGY METABOLISM AND LONGEVITY INC. ELEGANS

“…This is in accordance with Han et al and Jung et al, who previously found vanillic acid to promote thermogenesis in C57BL/6J mice and in primary cultured adipocytes [72,73].…”

Vanillic Acid Improves Comorbidity of Cancer and Obesity through STAT3 Regulation in High-Fat-Diet-Induced Obese and B16BL6 Melanoma-Injected Mice

“…VA is well-reported to exert anticancer activities in several types of cancers, including lymphocytes [20], leukemia [21], colon cancer [22], lung cancer [23], and also melanoma [19]. Moreover, we showed its anti-obesity effect in our previous study [24]. Since references support the potentially beneficial properties of VA in a comorbid situation of cancer and obesity, under this hypothesis, we establish a cancer-obesity comorbidity model (COC) of melanoma based on a study by Jung et al [7] and investigate the effect of VA focusing on the role of STAT3 pathway.…”

“…Two days after tumor inoculation, VA (10 mg/kg/day) was administered via oral gavage every other day, for two weeks, to one of the tumor-injected groups. The dose of VA was determined based on our previous study [24]. All groups were maintained with HFD administration.…”

Synergistic Effect of Bupleuri Radix and Scutellariae Radix on Adipogenesis and AMP‐Activated Protein Kinase: A Network Pharmacological Approach

“…Cytotoxicity of BR, SR, and BR-SR mixture was evaluated using the MTS assay, as previously described [23]. The absorbance was measured at 490 nm using a VERSAmax microplate reader (Molecular Devices, Sunnyvale, CA, USA).…”