Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0.02%, w/w). The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT) weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

The present study investigated the effects of soybean leaf extracts (SLEs) on blood glucose, insulin resistance, body fat and dyslipidemia in prediabetes subjects, and compared them with the effects of banaba extracts (BE) which is known to ameliorate diabetes in several animals and clinical studies. Overweight subjects with mild hyperglycemia (fasting blood glucose level of 100-125 mg dL(-1)) were randomly assigned to three groups and administered four capsules containing starch (2 g per day, Placebo), BE (300 mg per day, 0.3% corosolic acid) or SLE (2 g per day) during regular meals for 12 weeks. The SLE as well as BE significantly decreased the baseline-adjusted final blood glucose, HbA1c, HOMA-IR and transaminase levels compared to the placebo group. The body weight, BMI and WHR were not different between the groups, but the baseline-adjusted final body fat content and waist circumference were lower in the BE and SLE groups than in the placebo group. Furthermore, the baseline-adjusted final plasma triglyceride concentration was lower in the BE and SLE groups compared to the placebo group. There were no significant differences in plasma total cholesterol and LDL-cholesterol concentrations between the groups. However, the SLE, but not the BE, significantly increased the plasma HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol after 12 weeks of supplementation compared to the placebo group, while the atherogenic index was decreased. Taken together, these data suggest that SLE may play an important role in improving blood glucose, insulin resistance, adiposity, and dyslipidemia in prediabetes subjects consuming their habitual diet, similar to or better than BE.

We compared metabolic biomarkers in the blood and peripheral blood mononuclear cell (PBMC) gene expression profiles among normal weight (BMI, 18·5-23 kg/m 2 ), mildly obese (BMI, 25-27·5 kg/m 2 ) and moderately obese Korean adult men (BMI, 27·5-30 kg/m 2 ). High leptin, lipids (except LDL-and HDL-cholesterol) and apoB levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines and markers of insulin resistance, oxidative stress and liver damage were altered in moderately obese subjects but not in mildly obese subjects. PBMC transcriptome data showed enrichment of pathways involved in energy metabolism, insulin resistance, bone metabolism, cancer, inflammation and fibrosis in both mildly and moderately obese subjects. Signalling pathways involved in oxidative phosphorylation, TAG synthesis, carbohydrate metabolism and insulin production; mammalian target of rapamycin, forkhead box O, ras-proximate-1, RAS and transforming growth factor-β signalling; as well as extracellular matrix-receptor interaction were enriched only in moderately obese subjects, indicating that changes in PBMC gene expression profiles, according to metabolic disturbances, were associated with the development and/or aggravation of obesity. In particular, fourteen and fifteen genes differentially expressed only in mildly obese subjects and in both mildly and moderately obese subjects, respectively, could be used as early or stable biomarkers for diagnosing and treating obesity-associated metabolic disturbance. We characterised BMI-associated metabolic and molecular biomarkers in the blood and provided clues about potential blood-based targets for preventing or treating obesityrelated complications.

Green tea (GT) has various health effects, including anti-obesity properties. However, the multiple molecular mechanisms of the effects have not been fully determined. The aim of this study was to elucidate the anti-obesity effects of GT via the analysis of its metabolic and transcriptional responses based on RNA-seq profiles. C57BL/6J mice were fed a normal, high-fat (60% energy as fat), or high-fat + 0.25% (w/w) GT diet for 12 weeks. The GT extract ameliorated obesity, hepatic steatosis, dyslipidemia, and insulin resistance in diet-induced obesity (DIO) mice. GT supplementation resulted in body weight gain reduction than mice fed high-fat through enhanced energy expenditure, and reduced adiposity. The transcriptome profiles of epididymal white adipose tissue (eWAT) suggested that GT augments transcriptional responses to the degradation of branched chain amino acids (BCAAs), as well as AMP-activated protein kinase (AMPK) signaling, which suggests enhanced energy homeostasis. Our findings provide some significant insights into the effects of GT for the prevention of obesity and its comorbidities. We demonstrated that the GT extract contributed to the regulation of systemic metabolic homeostasis via transcriptional responses to not only lipid and glucose metabolism, but also amino acid metabolism via BCAA degradation in the adipose tissue of DIO mice.

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 (TXA2) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and TXA2, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

This study aimed to elucidate the molecular mechanism of Chrysanthemum morifolium Ramat. against obesity and diabetes, by comparing the transcriptional changes in epididymal white adipose tissue (eWAT) with those of the bioactive compound in C. morifolium, luteolin (LU). Male C57BL/6J mice were fed a normal diet, high-fat diet (HFD), and HFD supplemented with 1.5% w/w chrysanthemum leaf ethanol extract (CLE) for 16 weeks. Supplementation with CLE and LU significantly decreased the body weight gain and eWAT weight by stimulating mRNA expressions for thermogenesis and energy expenditure in eWAT via lipid mobilization, which may be linked to the attenuation of dyslipidemia. Furthermore, CLE and LU increased uncoupling protein-1 protein expression in brown adipose tissue, leading to energy expenditure. Of note, CLE and LU supplements enhanced the balance between lipid storage and mobilization in white adipose tissue (WAT), in turn, inhibiting adipocyte inflammation and lipotoxicity of peripheral tissues. Moreover, CLE and LU attenuated hepatic steatosis by suppressing hepatic lipogenesis, thereby ameliorating insulin resistance and dyslipidemia. Our data suggest that CLE helps inhibit obesity and its comorbidities via the complex interplay between liver and WAT in diet-induced obese mice.

The Platycodon grandiflorus root, a Korean medicinal food, is well known to have beneficial effects on obesity and diabetes. In this study, we demonstrated the metabolic effects of P. grandiflorus root ethanol extract (PGE), which is rich in platycodins, on diet-induced obesity. C57BL/6J mice (four-week-old males) were fed a normal diet (16.58% of kilocalories from fat), high-fat diet (HFD, 60% of kilocalories from fat), and HFD supplemented with 5% (w/w) PGE. In the HFD-fed mice, PGE markedly suppressed the body weight gain and white fat mass to normal control level, with simultaneous increase in the expression of thermogenic genes (such as SIRT1, PPARα, PGC1α, and UCP1), that accompanied changes in fatty acid oxidation (FAO) and energy expenditure. In addition, PGE improved insulin sensitivity through activation of the PPARγ expression, which upregulates adiponectin while decreasing leptin gene expression in adipocytes. Furthermore, PGE improved hepatic steatosis by suppressing hepatic lipogenesis while increasing expression of FAO-associated genes such as PGC1α. PGE normalized body fat and body weight, which is likely associated with the increased energy expenditure and thermogenic gene expression. PGE can protect from HFD-induced insulin resistance, and hepatic steatosis by controlling lipid and glucose metabolism.

Pterocarpans are known to have antifungal and anti-inflammatory properties. However, little is known about the changes in transcriptional profiles in response to a pterocarpan-high soybean leaf extract (PT). Therefore, this study investigated the effects of PT on blood glucose and lipid levels, as well as on the inflammation-related gene expression based on a peripheral blood mononuclear cells (PBMCs) mRNA sequencing analysis in Korean overweight and obese subjects with mild metabolic syndrome. The participants were randomly assigned to two groups and were administered either placebo (starch, 3 g/day) or PT (2 g/day) for 12 weeks. The PT intervention did not change body weight, body fat percentage and body mass index (BMI). However, PT significantly decreased the glycosylated hemoglobin (HbA1c), plasma glucose, free fatty acid, total cholesterol, and non-HDL cholesterol levels after 12 weeks. Furthermore, PT supplementation significantly lowered the homeostatic index of insulin resistance, as well as the plasma levels of inflammatory markers. Finally, the mRNA sequencing analysis revealed that PT downregulated genes related to immune responses. PT supplementation is beneficial for the improvement of metabolic syndrome by altering the fasting blood and plasma glucose, HbA1c, plasma lipid levels and inflammation-related gene expression in PBMCs.