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d-allulose is an uncommon sugar that provides almost no calories when consumed. Its sweetness is 70% that of sucrose. d-allulose is a metabolic regulator of glucose and lipid metabolism. However, few reports concerning its effect on diabetes and related metabolic disturbances in db/db mice are available. In this study, we evaluated d-allulose&rsquo, s effect on hyperglycemia, hyperinsulinemia, diabetes and inflammatory responses in C57BL/KsJ-db/db mice. Mice were divided into normal diet, erythritol supplemented (5% w/w), and d-allulose supplemented (5% w/w) groups. Blood glucose and plasma glucagon levels and homeostatic model assessment (HOMA-IR) were significantly lower in the d-allulose group than in the normal diet group, and plasma insulin level was significantly increased. Further, d-allulose supplement significantly increased hepatic glucokinase activity and decreased hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity. Expression of glucose transporter 4, insulin receptor substrate 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and AKT serine/threonine kinase 2 were also upregulated by d-allulose supplement in adipocyte and muscle. Finally, d-allulose effectively lowered plasma and hepatic triglyceride and free fatty acid levels, and simultaneously reduced hepatic fatty acid oxidation and carnitine palmitoyl transferase activity. These changes are likely attributable to suppression of hepatic fatty acid synthase and glucose-6-phosphate dehydrogenase activity. Notably, d-allulose also reduced pro-inflammatory adipokine and cytokine levels in plasma. Our results indicate that d-allulose is an effective sugar substitute for improving lipid and glucose metabolism.

Allulose has been reported to serve as an anti-obesity and anti-diabetic food component, however, its molecular mechanism is not yet completely understood. This study aims to elucidate the mechanisms of action for allulose in obesity-induced type 2 diabetes mellitus (T2DM), by analyzing the transcriptional and microbial populations of diet-induced obese mice. Thirty-six C57BL/6J mice were divided into four groups, fed with a normal diet (ND), a high-fat diet (HFD), a HFD supplemented with 5% erythritol, or a HFD supplemented with 5% allulose for 16 weeks, in a pair-fed manner. The allulose supplement reduced obesity and comorbidities, including inflammation and hepatic steatosis, and changed the microbial community in HFD-induced obese mice. Allulose attenuated obesity-mediated inflammation, by downregulating mRNA levels of inflammatory response components in the liver, leads to decreased plasma pro-inflammatory marker levels. Allulose suppressed glucose and lipid metabolism-regulating enzyme activities, ameliorating hepatic steatosis and improving dyslipidemia. Allulose improved fasting blood glucose (FBG), plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and the area under the curve (AUC) for the intraperitoneal glucose tolerance test (IPGTT), as well as hepatic lipid levels. Our findings suggested that allulose reduced HFD-induced obesity and improved T2DM by altering mRNA expression and the microbiome community.

Recently, there has been a global shift in diet towards an increased intake of energy-dense foods that are high in sugars. D-allulose has received attention as a sugar substitute and has been reported as one of the anti-obesity food components, however, its correlation with the intestinal microbial community is not yet completely understood. Thirty-six C57BL/6J mice were divided in to four dietary groups and fed a normal diet (ND), a high-fat diet (HFD, 20% fat, 1% cholesterol, w/w), and a HFD with 5% erythritol (ERY) and D-allulose (ALL) supplement for 16 weeks. A pair-feeding approach was used so that all groups receiving the high-fat diet would have the same calorie intake. As a result, body weight and body fat mass in the ALL group were significantly decreased toward the level of the normal group with a simultaneous decrease in plasma leptin and resistin. Fecal short-chain fatty acid (SCFA) production analysis revealed that ALL induced elevated total SCFA production compared to the other groups. Also, ALL supplement induced the change in the microbial community that could be responsible for improving the obesity based on 16S rRNA gene sequence analysis, and ALL significantly increased the energy expenditure in Day(6a.m to 6pm). Taken together, our findings suggest that 5% dietary ALL led to an improvement in HFD-induced obesity by altering the microbiome community.

The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD).The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain.Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver.Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.

cope 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 β-oxidation were downregulated by d-allulose to that of the normal group; however, in WAT, fatty acid synthase was decreased while β-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.

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)-1β, 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-1β 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.

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 β-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.

d-allulose is a rare sugar with zero energy that can be consumed by obese/overweight individuals. Many studies have suggested that zero-calorie d-allulose has beneficial effects on obesity-related metabolism in mouse models, but only a few studies have been performed on human subjects. Therefore, we performed a preliminary study with 121 Korean subjects (aged 20–40 years, body mass index ≥ 23 kg/m2). A randomized controlled trial involving placebo control (sucralose, 0.012 g × 2 times/day), low d-allulose (d-allulose, 4 g × 2 times/day), and high d-allulose (d-allulose, 7 g × 2 times/day) groups was designed. Parameters for body composition, nutrient intake, computed tomography (CT) scan, and plasma lipid profiles were assessed. Body fat percentage and body fat mass were significantly decreased following d-allulose supplementation. The high d-allulose group revealed a significant decrease in not only body mass index (BMI), but also total abdominal and subcutaneous fat areas measured by CT scans compared to the placebo group. There were no significant differences in nutrient intake, plasma lipid profiles, markers of liver and kidney function, and major inflammation markers among groups. These results provide useful information on the dose-dependent effect of d-allulose for overweight/obese adult humans. Based on these results, the efficacy of d-allulose for body fat reduction needs to be validated using dual energy X-ray absorption.

Scope The results of recent studies on d-allulose intervention in high-fat diet (HFD)-fed mice suggest that d-allulose has a substantial impact on obesity. In addition, several studies have uncovered bacterial candidates among the gut microbiota associated with obesity and inflammation in mice. To identify the d-allulose-attenuated genes related to the inflammation-associated bacterial candidates, two types of statistical analyses are performed. Methods and results Using liver and epididymal fat tissues, genes with expression levels that recovered from HFD-induced dysregulation are identified through differentially expressed gene (DEG) analysis. Finally, correlation-based network analysis between the diet, microbes, and the candidates identified from DEG analysis reveal 20 genes that showed anti-obesogenic patterns and associations with Lactobacillus and Coprococcus, which are representative bacterial candidates associated with inflammation and obesity. Conclusion The results of the present study suggest that d-allulose closely interacts with the candidate genes and microbes to alleviate weight gain and inflammation, partly via down regulation of Gm12250 expression in multiple tissues and increases the Lactobacillus and Coprococcus in gut microbiota composition.

D-allulose has recently received attention as a sugar substitute. However, there are currently no reports regarding its association with gastrointestinal (GI) tolerance. Thus, we performed a GI tolerance test for D-allulose in order to establish its daily acceptable intake level. When the dose of D-allulose was gradually increased in steps of 0.1 g/kg&middot, Body Weight (BW) to identify the maximum single dose for occasional ingestion, no cases of severe diarrhea or GI symptoms were noted until a dose of 0.4 g/kg&middot, BW was reached. Severe symptoms of diarrhea were noted at a dose of 0.5 g/kg&middot, BW. Similarly, the GI tolerance test did not show any incidences of severe diarrhea or GI symptoms until a dose of 0.5 g/kg&middot, BW was reached. A correlation analysis of the GI tolerance test for D-allulose and sugar revealed significantly higher frequencies of symptoms of diarrhea (p = 0.004), abdominal distention (p = 0.039), and abdominal pain (p = 0.031) after D-allulose intake. Increasing the total daily D-allulose intake gradually to 1.0 g/kg&middot, BW for regular ingestion resulted in incidences of severe nausea, abdominal pain, headache, anorexia, and diarrheal symptoms. Based on these results, we suggest a maximum single dose and maximum total daily intake of D-Allulose of 0.4 g/kg&middot, BW and 0.9 g/kg&middot, BW, respectively.