Anti-obesity effects of heat-transformed green tea extract through the activation of adipose tissue thermogenesis

Abstract

Background Adipose tissue thermogenesis is a potential therapeutic target to increase energy expenditure and thereby combat obesity. The aim of the present study was to investigate the thermogenic and anti-obesity effects of heat-transformed green tea extract (HTGT) and enzymatically modified isoquercetin (EMIQ). Methods Immortalized brown pre-adipocytes and C3H10T1/2 cells were used for in vitro analyses. A high-fat diet (HFD)-induced obesity mouse model and CIDEA-reporter mice were used for in vivo experiments. The effects of HTGT and EMIQ on mitochondrial metabolism were evaluated by immunoblot, mitochondrial staining, and oxygen consumption rate analyses. In vivo anti-obesity effects of HTGT and EMIQ were measured using indirect calorimetry, body composition analyses, glucose tolerance tests, and histochemical analyses. Results Co-treatment with HTGT and EMIQ (50 μg/mL each) for 48 h increased brown adipocyte marker and mitochondrial protein levels (UCP1 and COXIV) in brown adipocytes by 2.9-fold, while the maximal and basal oxygen consumption rates increased by 1.57- and 1.39-fold, respectively. Consistently, HTGT and EMIQ treatment increased the fluorescence intensity of mitochondrial staining in C3H10T1/2 adipocytes by 1.68-fold. The combination of HTGT and EMIQ (100 mg/kg each) increased the expression levels of brown adipocyte markers and mitochondrial proteins in adipose tissue. Two weeks of HTGT and EMIQ treatment (100 mg/kg each) led to a loss of 3% body weight and 7.09% of body fat. Furthermore, the treatment increased energy expenditure by 8.95% and improved glucose tolerance in HFD-fed mice. Conclusions The current study demonstrated that HTGT and EMIQ have in vivo anti-obesity effects partly by increasing mitochondrial metabolism in adipocytes. Our findings suggest that a combination of HTGT and EMIQ is a promising therapeutic agent for the treatment of obesity and related metabolic diseases.

Synergistic Effects of Heat-Treated Green Tea Extract and Enzymatically-Modified Isoquercitrin in Preventing Obesity

“…Epigallocatechin gallate (EGCG) is a prominent phytochemical found in green tea extract, and approximately half of EGCG undergoes epimerization to form gallocatechin gallate (GCG) during the heat treatment process [11]. A previous study demonstrated the effects of heat-treated green tea extract (HTGT) on visceral fat and hepatic triacylglycerol in rats [12], while our group confirmed that HTGT induces significantly higher expression of UCP1 in brown adipocytes, compared to green tea extract (GTE), due to its elevated content of GCG [13]. Enzymatically modified isoquercitrin (EMIQ) refers to the enzymatic derivatives of rutin, where glucose-rhamnose is attached to the position 3 of the quercetin glycosides [14,15].…”

“…In our previous study, we reported the anti-obesity effects of the combined treatment of HTGT and EMIQ. However, previous studies primarily focused on the short-term effects of the HTGT and EMIQ combination in terms of anti-obesity properties [13]. Furthermore, investigations into their in vivo synergistic effects and molecular mechanisms have been limited.…”

Potential of enhancing anti-obesogenic agriceuticals by applying sustainable fertilizers during plant cultivation

“…The co-treatment administered to HFD-induced obese mice also increased the expression of brown adipocyte markers and mitochondrial proteins in adipose tissue. After 2 weeks, mice lost 3% body weight and 7.09% body fat, while energy expenditure increased by 8.95% (Im et al, 2022). Bolin et al (2020) also found that a polyphenol-rich green tea extract induced thermogenesis in mice, decreased body weight, adipocyte size, and insulin resistance, increased energy expenditure, BAT thermogenesis, and stimulated browning in subcutaneous WAT.…”

Enzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms

“…In a recent study by Im et al [ 55 ] in mice also, a synergistic effect of EMIQ in combination with a heat-transformed green tea extract (100 + 100 mg/kg bw) was observed in the reduction of body weight, fat mass, and adipocyte size. The therapeutic effects were comparable to that of mirabegron (10 mg/kg bw), an agonist of the β3-AR signaling pathway, the primary regulatory mechanism involved in lipolysis.…”