Hepatic proteome and its network response to supplementation of an anti-obesity herbal mixture in diet-induced obese mice

Abstract

In the present study, we investigated the effects of multi-herbal water extract mixture, Taeumjowi-tang (TH) on liver proteome alteration in mice using twodimensional electrophoresis combined with MALDI-TOF-MS. Animals were fed high-fat diet with or without TH (0.3% wt/wt) supplement for 12 weeks. At the end of 5 th week of experimental diet, mice fed high-fat diet only were subdivided into 2 groups, obesity-prone (OP) and obesityresistant (OR) mice based on weight gain. OR mice gained less body weight compared to OP mice despite of same food intake. TH significantly suppressed weight gain, and proteomic analysis enabled the identification of 49 liver proteins showing differential regulation between OP and OR/TH mice. Combined results of proteomic and western blot analyses revealed decreased lipogenesis via three fatty acid metabolic targets (AMPK, ACC, and FAS) in livers of OR and TH mice. Using bioinformatic classification and network analysis, most of the identified proteins were classified as hydrolases, oxidoreductases, transferases, defense/immunity proteins, and enzyme modulators based on functional analysis of the PANTHER classification system. Combined results of proteomic and bioinformatic analyses using GeneMANIA identified two proteins (LACTB2 and NIT2) in the liver that potentially interact with fatty acid metabolic proteins. Furthermore, these proteins were included in acetylation, phosphoprotein, and metabolic processes in DAVID classification. These proteins were highly expressed in OP mice; however both their transcription and protein expression were lowered by TH treatment. In conclusion, combined data from proteomic and network analyses suggest that TH exerts anti-obesity effects by modulating fatty acid metabolic proteins/genes, particularly via the AMPK pathway. Most targeted proteins/ genes were modulated toward enhancing lipid metabolism in response to TH treatment.

Prediction of Efficacy of Taeumjowi-Tang for Treatment of Metabolic Risk Factors Based on Machine Learning

“…Taeumjowi-tang is a popular herbal product in Korea and is generally used for weight loss [6][7][8][9][10]32] and changes in several lipid profiles [6,11,13,14]. Until now, there have been no studies reporting prediction models or algorithms for the efficacy of Taeumjowi-tang or other herbal medicines for an individual.…”

“…However, several studies have examined the efficacy of Taeumjowi-tang. To examine the association of oral administration of Taeumjowitang with anthropometric and blood parameters, many studies have proven that the efficacy of Taeumjowi-tang is useful for weight reduction or changes in lipid profiles in humans and mice [6][7][8][9][10][11][12][13][14]. For example, Yoo et al [6] examined changes in anthropometric indices and blood parameters after dose intake of Taeumjowi-tang in obese Korean children.…”

“…Additionally, the efficacy of Taeumjowi-tang has been demonstrated in animal experiments. Several previous studies have examined the effect of Taeumjowitang for the treatment of obesity and its comorbidities in obese mice [7][8][9]. For example, Park et al [9] examined the efficacy of Taeumjowi-tang for the treatment of obesity and atopic dermatitis induced by a high-fat diet and 1-fluoro-2,4-dinitrobenzene in mice and suggested that Taeumjowi-tang was useful for the clinical management and treatment of comorbid obesity-atopic dermatitis because the effect may be caused by the regulation of HIF-1α expression.…”

“…Herbal medicines are often prescribed for obesity reduction. In traditional Korean medicine, Taeumjowi-tang is one of most well-known herbal medicines, and many studies have reported that Taeumjowi-tang is effective for weight reduction in humans and mice [6][7][8][9][10][11][12][13][14]. For example, for the assessment of efficacy and safety of Taeumjowi-tang, several studies have performed experiments to identify the changes in anthropometric indices and blood parameters such as body fat mass, weight, waist circumference, fasting glucose concentration, total cholesterol, HDL and LDL cholesterol levels, and triglyceride.…”

Differential proteomics for studying action mechanisms of traditional Chinese medicines

“…Another anti-obesity herbal medicine Taeumjowi-tang (TH) consisting of eight herbs has traditionally been used in Korea. Kim et al [40] identified the proteins differentially expressed in hepar of TH-treated obesity model rats utilizing proteomic and western blot analysis, and deduced that TH improved lipid metabolism through modulating fatty acid metabolizing proteins involved in obesity and hepatic injury, with the involvement of adenosine monophosphate-activated protein kinase, acetyl CoA carboxylase and fatty acid synthetase.…”