Cistanche tubulosa phenylethanoid glycosides suppressed adipogenesis in 3T3-L1 adipocytes and improved obesity and insulin resistance in high-fat diet induced obese mice

Abstract

Background Cistanche tubulosa is an editable and medicinal traditional Chinese herb and phenylethanoid glycosides are its major components, which have shown various beneficial effects such as anti-tumor, anti-oxidant and neuroprotective activities. However, the anti-obesity effect of C. tubulosa phenylethanoid glycosides (CTPG) and their regulatory effect on gut microbiota are still unclear. In the present study, we investigated its anti-obesity effect and regulatory effect on gut microbiota by 3T3-L1 cell model and obesity mouse model. Methods 3T3-L1 adipocytes were used to evaluate CTPG effects on adipogenesis and lipids accumulation. Insulin resistant 3T3-L1 cells were induced and used to measure CTPG effects on glucose consumption and insulin sensitivity. High-fat diet (HFD)-induced C57BL/6 obese mice were used to investigate CTPG effects on fat deposition, glucose and lipid metabolism, insulin resistance and intestinal microorganism. Results In vitro data showed that CTPG significantly decreased the triglyceride (TG) and non-esterified fatty acid (NEFA) contents of the differentiated 3T3-L1 adipocytes in a concentration-dependent manner without cytotoxicity, and high concentration (100 µg/ml) of CTPG treatment dramatically suppressed the level of monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 mature adipocytes. Meanwhile, CTPG increased glucose consumption and decreased NEFA level in insulin resistant 3T3-L1 cells. We further found that CTPG protected mice from the development of obesity by inhibiting the expansion of adipose tissue and adipocyte hypertrophy, and improved hepatic steatosis by activating AMPKα to reduce hepatic fat accumulation. CTPG ameliorated HFD-induced hyperinsulinemia, hyperglycemia, inflammation and insulin resistance by activating IRS1/Akt/GLUT4 insulin signaling pathway in white adipose tissue. Moreover, gut microbiota structure and metabolic functions in HFD-induced obese mice was changed by CTPG, especially short chain fatty acids-producing bacteria including Blautia, Roseburia, Butyrivibrio and Bacteriodes were significantly increased by CTPG treatment. Conclusions CTPG effectively suppressed adipogenesis and lipid accumulation in 3T3-L1 adipocytes and ameliorated HFD-induced obesity and insulin resistance through activating AMPKα and IRS1/AKT/GLUT4 signaling pathway and regulating the composition and metabolic functions of gut microbiota.

FGF19 Promotes the Proliferation and Insulin Secretion from Human Pancreatic β Cells Via the IRS1/GLUT4 Pathway

“…Additionally, they could also be utilized as diagnostic and prognostic markers. [30][31][32][33]. IRS1, a pivotal component of the insulin signaling pathway, along with GLUT4, a significant glucose transporter, are recognized for their contributions to maintaining glucose homeostasis and insulin sensitivity [34,35].…”

Variations in the Relative Abundance of Gut Bacteria Correlate with Lipid Profiles in Healthy Adults

“…M. timonensis is a recently described and poorly characterized species related to bacteria from the Faecalicatena genus from the Lachnospiraceae family [85]. The administration of plant-derived bioactive phenylethanoid glycosides increased the abundance of M. timonensis, concurrently decreasing total Ch, LDL, and HDL levels in a mouse model of obesity, suggesting a possible link between the species and circulating lipids [86]. In the current study, participants who reported a higher consumption of fibrerich foods such as fruits and legumes had a low relative abundance of this species.…”

A Novel Approach to Serving Plant-Based Confectionery—The Employment of Spray Drying in the Production of Carboxymethyl Cellulose-Based Delivery Systems Enriched with Teucrium montanum L. Extract

“…Among the identified hydroxybenzoic and hydroxycinnamic acids, flavones, and flavone glycosides [8][9][10], phenylethanoid glycosides (PGs) represent the most understudied phenolic group found in T. montanum extracts. The latest studies show that PGs are promising neuroprotective [11], anticancer [12], anti-obesity [13], anti-inflammatory [14], and antibacterial [15] agents. The highlighted antiviral properties of PGs, which act as natural inhibitors of SARS-CoV-2 protease, are already being used in China for COVID-19 treatment in the form of a patented TCM formulation-Lianhua Qingwen capsules [16,17].…”