Abstract
This study investigated whether decaffeinated green coffee bean extract prevents obesity and improves insulin resistance and elucidated its mechanism of action. Male C57BL/6N mice (N = 48) were divided into six dietary groups: chow diet, HFD, HFD-supplemented with 0.1%, 0.3%, and 0.9% decaffeinated green coffee bean extract, and 0.15% 5-caffeoylquinic acid. Based on the reduction in HFD-induced body weight gain and increments in plasma lipids, glucose, and insulin levels, the minimum effective dose of green coffee bean extract appears to be 0.3%. Green coffee bean extract resulted in downregulation of genes involved in WNT10b- and galanin-mediated adipogenesis and TLR4-mediated proinflammatory pathway and stimulation of GLUT4 translocation to the plasma membrane in white adipose tissue. Taken together, decaffeinated green coffee bean extract appeared to reverse HFD-induced fat accumulation and insulin resistance by downregulating the genes involved in adipogenesis and inflammation in visceral adipose tissue.
This study investigated whether decaffeinated green coffee bean extract prevents obesity and improves insulin resistance and elucidated its mechanism of action. Male C57BL/6N mice (N = 48) were divided into six dietary groups: chow diet, HFD, HFD-supplemented with 0.1%, 0.3%, and 0.9% decaffeinated green coffee bean extract, and 0.15% 5-caffeoylquinic acid. Based on the reduction in HFD-induced body weight gain and increments in plasma lipids, glucose, and insulin levels, the minimum effective dose of green coffee bean extract appears to be 0.3%. Green coffee bean extract resulted in downregulation of genes involved in WNT10b- and galanin-mediated adipogenesis and TLR4-mediated proinflammatory pathway and stimulation of GLUT4 translocation to the plasma membrane in white adipose tissue. Taken together, decaffeinated green coffee bean extract appeared to reverse HFD-induced fat accumulation and insulin resistance by downregulating the genes involved in adipogenesis and inflammation in visceral adipose tissue.
Introduction
Coffee is one of the most widely consumed beverages in the world, and therefore the potential health consequences of coffee consumption are of great public interest. Heavy coffee drinking may result in sleep disorders, hypokalemia, and cardiac arrhythmias. At the same time, several epidemiologic studies have reported that the risk of Parkinson's disease, Alzheimer's disease, and certain types of cancer is reduced in regular coffee consumers. In addition, coffee has recently received scientific attention as current epidemiologic and in vivo studies have revealed its health benefits against obesity and metabolic disorders, especially type 2 diabetes. These health advantages are mostly derived from chlorogenic acids contained in coffee beans.
Adipogenesis is a process of mesenchymal precursor cells differentiating into adipocytes where peroxisome proliferator-activated receptor γ2 (PPARγ2) and CCAAT/enhancer-binding protein α (C/EBPα) are the master transcriptional regulators. Downstream targets for PPARγ2 include adipocyte lipid binding protein (aP2), cluster of differentiation (CD), lipoprotein lipase (LPL), and fatty acid synthase (FAS), which together induce lipid accumulation and metabolism. Thus, inactivation of these adipogenic regulators may be a novel way to suppress adipogenesis and ultimately prevent obesity.
Another critical aspect of adipose tissue is that it serves as an endocrine organ, releasing biologically active adipokines. Toll-like receptor (TLR) 2 and TLR4 induce the expression of a large number of proinflammatory target genes. It was recently discovered that TLR4 can sense free fatty acids (FFAs) engaging proinflammatory pathways that lead to secretion of cytokines. Furthermore, several studies have demonstrated a causative relationship between inflammation and insulin resistance. JNK, especially, serves as a main mediator that leads to insulin resistance by impairing GLUT4 translocation. Thus, reducing the FFA level in blood and peripheral tissues such as the adipose tissue and muscles might result in therapeutic effects against obesity by attenuating not only adipogenesis but also inflammation and insulin resistance.
Raw coffee beans are rich in chlorogenic acids and caffeine, and their contents in coffee beans are significantly decreased during the roasting and decaffeination processes. Green coffee bean extract used in the present study is prepared from decaffeinated and unroasted coffee beans, making it a novel source of chlorogenic acids and eliminating the possible side effects of caffeine. There is no report on toxicological studies on green coffee bean extract. In a clinical trial, decaffeinated green coffee bean extract induced weight loss in overweight volunteers, provided with 400 mg/day for 60 days. Yet, further investigation on toxic dose of green coffee bean extract is required in animal models. Cho et al. revealed that 5-caffeoylquinic acid (CQA), a representative chlorogenic acid in green coffee beans, exhibits antiobesity properties in mice fed a HFD. Another study reported that decaffeinated green coffee bean extract, delivered through drinking water for 20 weeks, significantly improved HFD-induced insulin resistance in mice; however, the dose delivered to mice was not clearly indicated and its molecular mechanism on improving insulin sensitivity has not been examined. Also, the antiobesity effect of decaffeinated green coffee bean extract has not yet been reported in HFD-induced obese mice. Therefore, the aims of this study were to investigate whether decaffeinated green coffee bean extract exerts protective effects against visceral obesity and insulin resistance in mice fed a HFD and to evaluate whether these effects are derived from 5-CQA. Furthermore, we explored the potential molecular mechanisms of the health benefits of decaffeinated green coffee bean extract, focusing on the gene expression involved in adipogenesis and insulin resistance in white adipose tissue (WAT).
Resource: http://www.ncbi.nlm.nih.gov
Coffee is one of the most widely consumed beverages in the world, and therefore the potential health consequences of coffee consumption are of great public interest. Heavy coffee drinking may result in sleep disorders, hypokalemia, and cardiac arrhythmias. At the same time, several epidemiologic studies have reported that the risk of Parkinson's disease, Alzheimer's disease, and certain types of cancer is reduced in regular coffee consumers. In addition, coffee has recently received scientific attention as current epidemiologic and in vivo studies have revealed its health benefits against obesity and metabolic disorders, especially type 2 diabetes. These health advantages are mostly derived from chlorogenic acids contained in coffee beans.
Adipogenesis is a process of mesenchymal precursor cells differentiating into adipocytes where peroxisome proliferator-activated receptor γ2 (PPARγ2) and CCAAT/enhancer-binding protein α (C/EBPα) are the master transcriptional regulators. Downstream targets for PPARγ2 include adipocyte lipid binding protein (aP2), cluster of differentiation (CD), lipoprotein lipase (LPL), and fatty acid synthase (FAS), which together induce lipid accumulation and metabolism. Thus, inactivation of these adipogenic regulators may be a novel way to suppress adipogenesis and ultimately prevent obesity.
Another critical aspect of adipose tissue is that it serves as an endocrine organ, releasing biologically active adipokines. Toll-like receptor (TLR) 2 and TLR4 induce the expression of a large number of proinflammatory target genes. It was recently discovered that TLR4 can sense free fatty acids (FFAs) engaging proinflammatory pathways that lead to secretion of cytokines. Furthermore, several studies have demonstrated a causative relationship between inflammation and insulin resistance. JNK, especially, serves as a main mediator that leads to insulin resistance by impairing GLUT4 translocation. Thus, reducing the FFA level in blood and peripheral tissues such as the adipose tissue and muscles might result in therapeutic effects against obesity by attenuating not only adipogenesis but also inflammation and insulin resistance.
Raw coffee beans are rich in chlorogenic acids and caffeine, and their contents in coffee beans are significantly decreased during the roasting and decaffeination processes. Green coffee bean extract used in the present study is prepared from decaffeinated and unroasted coffee beans, making it a novel source of chlorogenic acids and eliminating the possible side effects of caffeine. There is no report on toxicological studies on green coffee bean extract. In a clinical trial, decaffeinated green coffee bean extract induced weight loss in overweight volunteers, provided with 400 mg/day for 60 days. Yet, further investigation on toxic dose of green coffee bean extract is required in animal models. Cho et al. revealed that 5-caffeoylquinic acid (CQA), a representative chlorogenic acid in green coffee beans, exhibits antiobesity properties in mice fed a HFD. Another study reported that decaffeinated green coffee bean extract, delivered through drinking water for 20 weeks, significantly improved HFD-induced insulin resistance in mice; however, the dose delivered to mice was not clearly indicated and its molecular mechanism on improving insulin sensitivity has not been examined. Also, the antiobesity effect of decaffeinated green coffee bean extract has not yet been reported in HFD-induced obese mice. Therefore, the aims of this study were to investigate whether decaffeinated green coffee bean extract exerts protective effects against visceral obesity and insulin resistance in mice fed a HFD and to evaluate whether these effects are derived from 5-CQA. Furthermore, we explored the potential molecular mechanisms of the health benefits of decaffeinated green coffee bean extract, focusing on the gene expression involved in adipogenesis and insulin resistance in white adipose tissue (WAT).
Resource: http://www.ncbi.nlm.nih.gov
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