Antiobesity Effects of Short-Chain Chitosan in Diet-Induced Obese Mice.

Dietary chitosan is known for its antiobesity effects by combining with bile acid and lipid droplets. When the chitosan structure is broken into short chains, the fat-binding capacity increases. The aim of this study was to compare long-chain chitosan (LC) with short-chain chitosan (SC) for their antiobesity effects in high-fat diet (HFD)-induced obese C57BL/6J mice for 12 weeks. The body weights of mice in both chitosan groups were decreased, especially in the SC group compared with the LC group. Total white adipose tissue and visceral fat weights were also decreased in mice of the SC group more than those of the HFD group. Moreover, SC supplementation lowered plasma triglyceride (TG) and cholesterol levels, whereas LC only lowered plasma free fatty acid level. Fecal lipids were increased in mice of both LC and SC groups, and hepatic TG and cholesterol levels were decreased in both groups. SC lowered phosphatidate phosphohydrolase activity and elevated ß-oxidation in the liver. Furthermore, SC decreased the expression of the hepatic lipid-regulating genes, including fatty acid synthase, peroxisome proliferator-activated receptor (PPAR)γ1, and PPARγ2; and increased the expression of carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor γ coactivator (PGC)1α genes. In conclusion, we demonstrated that long-term supplementation of SC can ameliorate body weight and lipid levels by increasing lipid excretion and regulating lipid metabolism, including some enzyme activities and gene expression levels, in HFD-induced obese mice.

Seabuckthorn Leaves Extract and Flavonoid Glycosides Extract from Seabuckthorn Leaves Ameliorates Adiposity, Hepatic Steatosis, Insulin Resistance, and Inflammation in Diet-Induced Obesity.

The aim of the current study was to elucidate the effect of seabuckthorn leaves (SL) extract and flavonoid glycosides extract from seabuckthorn leaves (SLG) on diet-induced obesity and related metabolic disturbances, and additionally, to identify whether flavonoid glycosides and other components in SL can exert a possible interaction for the prevention of metabolic diseases by comparing the effect of SL and SLG. C57BL/6J mice were fed a normal diet (ND, AIN-93G purified diet), high-fat diet (HFD, 60 kcal% fat), HFD + 1.8% (w/w) SL (SL), and HFD + 0.04% (w/w) SLG (SLG) for 12 weeks. In high fat-fed mice, SL and SLG decreased the adiposity by suppressing lipogenesis in adipose tissue, while increasing the energy expenditure. SL and SLG also improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption, whilst also enhancing hepatic fatty acid oxidation, which may be linked to the improvement in dyslipidemia. Moreover, SL and SLG improved insulin sensitivity by suppressing the levels of plasma GIP that were modulated by secreted resistin and pro-inflammatory cytokine, and hepatic glucogenic enzyme activities. SL, especially its flavonoid glycosides (SLG), can protect against the deleterious effects of diet-induced obesity (DIO) and its metabolic complications such as adiposity, dyslipidemia, inflammation, hepatic steatosis, and insulin resistance.

Metabolic Effect of an Oriental Herbal Medicine on Obesity and Its Comorbidities with Transcriptional Responses in Diet-Induced Obese Mice.

Taeeumjowuitang (TJ) is an alternative herbal medicine that has been used to treat obesity in Korea. The molecular mechanisms involved in TJ-induced anti-obesity effects have not yet been determined. The aim of the current study was to elucidate the effects of TJ on obesity and metabolic syndrome, by analyzing the transcriptional and metabolic responses to TJ treatment. C57BL/6J mice were fed a high-fat or high-fat + 3% (w/w) TJ diet for 12 weeks. Their phenotypic characteristics were measured and the anti-obesity mechanism was elucidated, based on the RNA sequencing (RNA-seq) transcriptomic profiles in an animal model of obesity. TJ treatment ameliorated insulin resistance, dyslipidemia, and hepatic steatosis in high-fat diet-induced obese mice, with a simultaneous reduction in body weight gain by enhancing energy expenditure and suppressing adiposity. An analysis of the global transcriptional changes by RNA-seq revealed that TJ upregulated mitochondrial oxidative phosphorylation-associated genes in epididymal white adipose tissue (eWAT), suggesting an enhanced mitochondrial function after TJ treatment. Moreover, TJ effectively attenuated the high-fat diet-induced inflammatory response through transcriptional changes in eWAT. Our findings provide some mechanistic insights into the effects of TJ, an alternative oriental medicine, in the treatment of obesity and its comorbidities. They demonstrate that metabolic and transcriptional responses to diet-induced obesity with TJ treatment were desirable in adipose tissue metabolism.

Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome in Overweight and Obese Korean Subjects: Randomized Controlled Trial.

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.

Effect of Green Tea Extract on Systemic Metabolic Homeostasis in Diet-Induced Obese Mice Determined via RNA-Seq Transcriptome Profiles.

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.

Platycodon grandiflorus Root Extract Attenuates Body Fat Mass, Hepatic Steatosis and Insulin Resistance through the Interplay between the Liver and Adipose Tissue.

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.

d-Allulose supplementation normalized the body weight and fat-pad mass in diet-induced obese mice via the regulation of lipid metabolism under isocaloric fed condition.

SCOPE: A number of findings suggest that zero-calorie d-allulose, also known as d-psicose, has beneficial effects on obesity-related metabolic disturbances. However, it is unclear whether d-allulose can normalize the metabolic status of diet-induced obesity without having an impact on the energy density. We investigated whether 5% d-allulose supplementation in a high fat diet(HFD) could normalize body fat in a diet-induced obesity animal model under isocaloric pair-fed conditions. METHODS AND RESULTS: Mice were fed an HFD with or without various sugar substitutes (d-glucose, d-fructose, erytritol, or d-allulose, n = 10 per group) for 16 wk. Body weight and fat-pad mass in the d-allulose group were dramatically lowered to that of the normal group with a simultaneous decrease in plasma leptin and resistin concentrations. d-allulose lowered plasma and hepatic lipids while elevating fecal lipids with a decrease in mRNA expression of CD36, ApoB48, FATP4, in the small intestine in mice. In the liver, activities of both fatty acid synthase and ß-oxidation were downregulated by d-allulose to that of the normal group; however, in WAT, fatty acid synthase was decreased while ß-oxidation activity was enhanced. CONCLUSION: Taken together, our findings suggest that 5% dietary d-allulose led to the normalization of the metabolic status of diet-induced obesity by altering lipid-regulating enzyme activities and their gene-expression level along with fecal lipids.

Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet.

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.

Combined Supplementation with Grape Pomace and Omija Fruit Ethanol Extracts Dose-Dependently Improves Body Composition, Plasma Lipid Profiles, Inflammatory Status, and Antioxidant Capacity in Overweight and Obese Subjects.

The aim of this study was to examine the efficacy of combined grape pomace and omija fruit ethanol extracts (GO) on metabolic disorders in overweight or obese subjects. Seventy-six subjects (30-70 years, body mass index ≥23.0 kg/m2) were divided into control (starch, 4 g/day, n = 24), low-GO (low dose GO, grape pomace extract [342.5 mg/day] + omija fruit extract [57.5 mg/day], n = 26), and high-GO (high dose GO, grape pomace extract [685 mg/day] + omija fruit extract [115 mg/day], n = 26) groups. Body composition, nutrient intake, plasma lipid profiles, inflammation, antioxidant capacity, and hepatotoxicity markers were assessed in all subjects at the baseline and 10 weeks after taking the supplements. The body weight and body fat of overweight or obese subjects was not significantly altered in the low-GO and high-GO groups. However, the high-GO supplement significantly decreased the baseline-adjusted final plasma total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-high-density lipoprotein (HDL)-cholesterol levels and increased the baseline-adjusted final plasma apolipoprotein (apo) A-1 level compared with that of the control group. In addition, the high-GO supplement significantly lowered apo B, apo B/apo A-1, lipoprotein a (Lp[a]), atherogenic index, interleukin (IL)-1ß, tumor necrosis factor-α, and elevated erythrocyte antioxidant capacity compared with the control group or the baseline levels. The low-GO supplement decreased the plasma IL-1ß level and elevated erythrocyte superoxide dismutase activity compared with that at baseline. However, in general, high-GO exerted a greater effect than low-GO. There were no significant differences in activities of plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase between the groups. This study is a preliminary clinical study to verify that GO could be beneficial for amelioration of obesity-related dyslipidemia, inflammation, and oxidative stress without side effect in the overweight or obese subjects.

Effects of the Combined Extracts of Grape Pomace and Omija Fruit on Hyperglycemia and Adiposity in Type 2 Diabetic Mice.

Grape products have been known to exert greater antioxidant and anti-obesity than anti-hyperglycemic effects in animals and humans. Omija is used as an ingredient in traditional medicine, and it is known to have an anti-hyperglycemic effect. We investigated whether the combined extracts of grape pomace and omija fruit (GE+OE) could reduce fat accumulation in adipose and hepatic tissues and provide beneficial effects against hyperglycemia and insulin resistance in type 2 diabetic mice. C57BL/KsJ-db/db mice were fed either a normal control diet or GE+OE (0.5% grape pomace extract and 0.05% omija fruit extract, w/w) for 7 weeks. GE+OE decreased plasma leptin and resistin levels while increasing adiponectin levels and reducing the total white adipose tissue weight. Furthermore, GE+OE lowered plasma free fatty acid (FFA), triglyceride, and total-cholesterol levels as well as hepatic FFA and cholesterol levels. Hepatic fatty acid synthase and glucose 6-phosphate dehydrogenase activities were decreased in the GE+OE group, whereas hepatic ß-oxidation activity was increased. Furthermore, GE+OE supplementation not only reduced hyperglycemia and pancreatic ß-cell failure but also lowered blood glycosylated hemoglobin and plasma insulin levels. The homeostasis model assessment of insulin resistance levels was also decreased and the decrease seems to be mediated by the lowered activities of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinases. The present data suggest that GE+OE may have the potential to reduce hyperglycemia, insulin resistance, and obesity in patients with type 2 diabetes.

The beneficial effects of combined grape pomace and omija fruit extracts on hyperglycemia, adiposity and hepatic steatosis in db/db mice: a comparison with major index compounds.

This study investigated the effects of combined grape pomace and omija fruit extracts (GO) on diabetes-related metabolic changes in type 2 diabetic db/db mice. The effects of GO were compared with those of a resveratrol and schizandrin mixture (RS), which is a mixture of major components of GO. Mice were fed a normal diet with RS (0.005% resveratrol and 0.02% schizandrin in diet, w/w) or GO (0.3% grape pomace ethanol extract and 0.05% omija fruit ethanol extract in diet, w/w) for seven weeks. RS and GO not only lowered the levels of blood and plasma glucose, HbA1c, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) with a simultaneous decrease in hepatic gluconeogenic enzymes activities and adiposity, but also improved preservation of the pancreatic ß-cells. Plasma leptin and resistin levels were lower while the plasma adiponectin level was higher in the RS and GO groups than in the control group. Especially, GO increased hepatic glucokinase activity and gene expression and improved hepatic steatosis by elevating fatty acid oxidation compared to RS. These findings suggest that GO ameliorates hyperglycemia, adiposity and hepatic steatosis in type 2 diabetic mice.

Combined ethanol extract of grape pomace and omija fruit ameliorates adipogenesis, hepatic steatosis, and inflammation in diet-induced obese mice.

The aim of this study was to evaluate the long-term effects of grape pomace ethanol extract (GPE) with or without omija fruit ethanol extract (OFE) on adiposity, hepatic steatosis, and inflammation in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD) as the control diet and HFD plus GPE (0.5%, w/w) with or without OFE (0.05%, w/w) as the experimental diet for 12 weeks. GPE alone did not significantly affect adipogenesis and hepatic steatosis. However, the supplementation of GPE + OFE significantly lowered body weight gain, white adipose tissue weight, adipocyte size, and plasma free fatty acid and adipokines (leptin, PAI-1, IL-6, and MCP-1) levels in HFD-fed mice compared to those of the control group. These beneficial effects of GPE + OFE were partly related to the decreased expression of lipogenic and inflammatory genes in white adipose tissue. GPE + OFE supplementation also significantly lowered liver weight and ameliorated fatty liver by inhibiting expression of hepatic genes involved in fatty acid and cholesterol syntheses as well as inflammation and by activating hepatic fatty acid oxidation. These findings suggest that the combined ethanol extract of grape pomace and omija fruit has the potential to improve adiposity and fatty liver in diet-induced obese mice.

Citrus unshiu peel extract ameliorates hyperglycemia and hepatic steatosis by altering inflammation and hepatic glucose- and lipid-regulating enzymes in db/db mice.

Insulin resistance in Type 2 diabetes leads to hepatic steatosis that can accompanied by progressive inflammation of the liver. Citrus unshiu peel is a rich source of citrus flavonoids that possess anti-inflammatory, anti-diabetic and lipid-lowering effects. However, the ability of citrus unshiu peel ethanol extract (CPE) to improve hyperglycemia, adiposity and hepatic steatosis in Type 2 diabetes is unknown. Thus, we evaluated the effects of CPE on markers for glucose, lipid metabolism and inflammation in Type 2 diabetic mice. Male C57BL/KsJ-db/db mice were fed a normal diet with CPE (2 g/100 g diet) or rosiglitazone (0.001 g/100 g diet) for 6 weeks. Mice supplemented with the CPE showed a significant decrease in body weight gain, body fat mass and blood glucose level. The antihyperglycemic effect of CPE appeared to be partially mediated through the inhibition of hepatic gluconeogenic phosphoenolpyruvate carboxykinase mRNA expression and its activity and through the induction of insulin/glucagon secretion. CPE also ameliorated hepatic steatosis and hypertriglyceridemia via the inhibition of gene expression and activities of the lipogenic enzymes and the activation of fatty acid oxidation in the liver. These beneficial effects of CPE may be related to increased levels of anti-inflammatory adiponectin and interleukin (IL)-10, and decreased levels of pro-inflammatory markers (IL-6, monocyte chemotactic protein-1, interferon-γ and tumor necrosis factor-α) in the plasma or liver. Taken together, we suggest that CPE has the potential to improve both hyperglycemia and hepatic steatosis in Type 2 diabetes.

Modulation of lipid metabolism by polyphenol-rich grape skin extract improves liver steatosis and adiposity in high fat fed mice.

This study investigated the influence of polyphenol-rich grape skin extract (GSE) on adiposity and hepatic steatosis in mice fed a high fat diet (HFD) and its underlying mechanisms based on adipose and hepatic lipid metabolism. C57BL/6J mice were fed a normal diet or a HFD (20% fat, w/w) with or without GSE (0.15%, w/w) for 10 weeks. The supplementation of GSE significantly lowered body weight, fat weight, plasma free fatty acid level, and hepatic lipid accumulation compared to the HFD group. Plasma leptin level was significantly lower, while the plasma adiponectin level was higher in the GSE group than in the HFD group. GSE supplementation significantly suppressed the activities of lipogenic enzymes in both adipose and liver tissues, which was concomitant with ß-oxidation activation. Furthermore, GSE reversed the HFD-induced changes of the expression of genes involved in lipogenesis and ß-oxidation in the liver. These findings suggest that GSE may protect against diet-induced adiposity and hepatic steatosis by regulating mRNA expression and/or activities of enzymes that regulate lipogenesis and fatty acid oxidation in the adipose tissue and liver.