Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

Abstract

Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from Echinacea angustifolia , and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca 2+ signaling proteins as well as intracellular Ca 2+ levels were also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process via the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet

“…Previous studies indicated that the specific knockout of HIF-2α in mice could disturb the intestinal lactic acid level, thereby decreasing the abundance of Bacteroides and increasing that of rumen cocci, which resulted in promoting the levels of taurocholic acid and deoxycholic acid ( Wu et al., 2021 ). These acids could activate the adipose G-protein-coupled bile acid receptor and upregulate the expression of UCP1 and CKMT2 , increasing heat production in white adipose tissue ( Haddish and Yun, 2023 ). Clostridium butyricum CCFM1299 could reduce obesity by increasing energy expenditure and regulating host bile acid metabolism ( Liao et al., 2023 ).…”

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“…Previous studies indicated that the specific knockout of HIF-2a in mice could disturb the intestinal lactic acid level, thereby decreasing the abundance of Bacteroides and increasing that of rumen cocci, which resulted in promoting the levels of taurocholic acid and deoxycholic acid (Wu et al, 2021). These acids could activate the adipose G-protein-coupled bile acid receptor and upregulate the expression of UCP1 and CKMT2, increasing heat production in white adipose tissue (Haddish and Yun, 2023). Clostridium butyricum CCFM1299 could reduce obesity by increasing energy expenditure and regulating host bile acid metabolism (Liao et al, 2023).…”