Oxidative Stress and Left Ventricular Performance in Patients with Different Glycometabolic Phenotypes

The aim of the present study was to evaluate the possible correlation between oxidative stress and subclinical myocardial damage, assessed with speckle tracking echocardiography (STE), in normal glucose tolerance (NGT) patients with one-hour plasma glucose values ≥ 155 mg/dL (NGT ≥ 155), comparing them to NGT < 155 subjects, impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) newly diagnosed patients. We enrolled 100 Caucasian patients. All subjects underwent OGTT. The serum values of oxidative stress markers (8-isoprostane and Nox-2) were assessed with an ELISA test. Echocardiographic recordings were performed using an E-95 Pro ultrasound system. We observed significant differences, among the four groups, for fasting plasma glucose (p < 0.0001), one-hour postload (p < 0.0001), and two-hour postload plasma glucose (p < 0.0001). As compared with NGT < 155, NGT ≥ 155 exhibited significantly worse insulin sensitivity and higher values of hs-CRP. No significant differences were observed between NGT ≥ 155 and IGT patients. There was a significant increase in 8-isoprostane (p < 0.0001) and Nox-2 (p < 0.0001), from the first to fourth group, indicating an increase in oxidative stress with the worsening of the metabolic status. Serum levels of 8-isoprostane and Nox-2 were significantly increased in NGT ≥ 155 compared to the NGT < 155 group, but similar to IGT. The global longitudinal strain (GLS) appeared progressively lower proceeding from the NGT < 155 to T2DM group (p < 0.0001). For similar values of left ventricular ejection fraction (LVEF), NGT ≥ 155 exhibited reduced GLS compared to NGT < 155 (p = 0.001), but similar to IGT patients. Our study demonstrated that NGT ≥ 155 subjects exhibit early functional impairment of myocardial contractile fibres, these alterations are correlated with increased oxidative stress.     

Changes in Plasma Metabolome Profiles Following Oral Glucose Challenge among Adult Chinese

Little is known about changes in plasma metabolome profiles during the oral glucose tolerance test (OGTT) in Chinese. We aimed to characterize plasma metabolomic profiles at 0 and 2 h of OGTT and their changes in individuals of different glycemic statuses. A total of 544 metabolites were detected at 0 and 2 h of OGTT by a nontarget strategy in subjects with normal glucose (n = 234), prediabetes (n = 281), and newly diagnosed type 2 diabetes (T2D) (n = 66). Regression model, mixed model, and partial least squares discrimination analysis were applied. Compared with subjects of normal glucose, T2D cases had significantly higher levels of glycerone at 0 h and 22 metabolites at 2 h of OGTT (false discovery rate (FDR) < 0.05, variable importance in projection (VIP) > 1). Seven of the twenty-two metabolites were also significantly higher in T2D than in prediabetes subjects at 2 h of OGTT (FDR < 0.05, VIP > 1). Two hours after glucose challenge, concentrations of 35 metabolites (normal: 18; prediabetes: 23; T2D: 13) significantly increased (FDR < 0.05, VIP > 1, fold change (FC) > 1.2), whereas those of 45 metabolites (normal: 36; prediabetes: 29; T2D: 18) significantly decreased (FDR < 0.05, VIP > 1, FC < 0.8). Distinct responses between cases and noncases were detected in metabolites including 4-imidazolone-5-acetate and 4-methylene-L-glutamine. More varieties of distinct metabolites across glycemic statuses were observed at 2 h of OGTT compared with fasting state. Whether the different patterns and responsiveness of certain metabolites in T2D reflect a poor resilience of specific metabolic pathways in regaining glucose homeostasis merits further study.     

Apple-Derived Pectin Modulates Gut Microbiota,Improves Gut Barrier Function,and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity

This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats.     

Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (−39.1%) and fat weight (−26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (−20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder’s functional and health-promoting benefits associated with anti-obesity and antidiabetes.     

High Fat Diet Exposure during Fetal Life Enhances Plasma and Hepatic Omega-6 Fatty Acid Profiles in Fetal Wistar Rats

Pregnant rats were fed a high fat diet (HFD) for the first (HF1), second (HF2), third (HF3) or all three weeks (HFG) of gestation. Maintenance on a HFD during specific periods of gestation was hypothesized to alter fetal glycemia, insulinemia, induce insulin resistance; and alter fetal plasma and hepatic fatty acid (FA) profiles. At day 20 of gestation, fetal plasma and hepatic FA profiles were determined by gas chromatography; body weight, fasting glycemia, insulinemia and the Homeostasis Model Assessment (HOMA-insulin resistance) were also determined. HF3 fetuses were heaviest concomitant with elevated glycemia and insulin resistance (p < 0.05). HFG fetuses had elevated plasma linoleic (18:2 n-6) and arachidonic (20:4 n-6) acid proportions (p < 0.05). In the liver, HF3 fetuses displayed elevated linoleic, eicosatrienoic (20:3 n-6) and arachidonic acid proportions (p < 0.05). HFG fetuses had reduced hepatic docosatrienoic acid (22:5 n-3) proportions (p < 0.05). High fat maintenance during the final week of fetal life enhances hepatic omega-6 FA profiles in fetuses concomitant with hyperglycemia and insulin resistance thereby presenting a metabolically compromised phenotype.     

A Potential Synbiotic Strategy for the Prevention of Type 2 Diabetes: Lactobacillus paracasei JY062 and Exopolysaccharide Isolated from Lactobacillus plantarum JY039

The disturbance of intestinal microorganisms and the exacerbation of type 2 diabetes (T2D) are mutually influenced. In this study, the effect of exopolysaccharides (EPS) from Lactobacillus plantarum JY039 on the adhesion of Lactobacillus paracasei JY062 was investigated, as well as their preventive efficacy against T2D. The results showed that the EPS isolated from L. plantarum JY039 effectively improved the adhesion rate of L. paracasei JY062 to Caco-2 cells (1.8 times) and promoted the proliferation of L. paracasei JY062. In the mice experiment, EPS, L. paracasei JY062 and their complex altered the structure of the intestinal microbiota, which elevated the proportion of Bifidobacterium, Faecalibaculum, while inversely decreasing the proportion of Firmicutes, Muribaculaceae, Lachnospiraceae and other bacteria involved in energy metabolism (p < 0.01; p < 0.05); enhanced the intestinal barrier function; promoted secretion of the gut hormone peptide YY (PYY) and glucagon-like peptide-1 (GLP-1); and reduced inflammation by balancing pro-inflammatory factors IL-6, TNF-α and anti-inflammatory factor IL-10 (p < 0.01; p < 0.05). These results illustrate that EPS and L. paracasei JY062 have the synbiotic potential to prevent and alleviate T2D.     

Association between Hyperglycemia at Hospital Presentation and Hospital Outcomes in COVID-19 Patients with and without Type 2 Diabetes: A Retrospective Cohort Study of Hospitalized Inner-City COVID-19 Patients

This study aimed to determine the relationships among hyperglycemia (HG), the presence of type 2 diabetes (T2D), and the outcomes of COVID-19. Demographic data, blood glucose levels (BG) measured on admission, and hospital outcomes of COVID-19 patients hospitalized at Boston University Medical Center from 1 March to 4 August 2020 were extracted from the hospital database. HG was defined as BG > 200 mg/dL. Patients with type 1 diabetes or BG < 70 mg/dL were excluded. A total of 458 patients with T2D and 976 patients without T2D were included in the study. The mean ± SD age was 56 ± 17 years and 642 (45%) were female. HG occurred in 193 (42%) and 42 (4%) of patients with and without T2D, respectively. Overall, the in-hospital mortality rate was 9%. Among patients without T2D, HG was statistically significantly associated with mortality, ICU admission, intubation, acute kidney injury, and severe sepsis/septic shock, after adjusting for potential confounders (p < 0.05). However, only ICU admission and acute kidney injury were associated with HG among patients with T2D (p < 0.05). Among the 235 patients with HG, the presence of T2D was associated with decreased odds of mortality, ICU admission, intubation, and severe sepsis/septic shock, after adjusting for potential confounders, including BG (p < 0.05). In conclusion, HG in the subset of patients without T2D could be a strong indicator of high inflammatory burden, leading to a higher risk of severe COVID-19.     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Effect of Stay-Green Wheat,a Novel Variety of Wheat in China,on Glucose and Lipid Metabolism in High-Fat Diet Induced Type 2 Diabetic Rats

The use of natural hypoglycemic compounds is important in preventing and managing Type 2 diabetes mellitus (T2DM). Forty male Sprague-Dawley rats weighing 150–180 g were divided into four groups to investigate the effects of the compounds in stay-green wheat (SGW), a novel variety of wheat in China, on T2DM rats. The control group (NDC) was fed with a standard diet, while T2DM was induced in the rats belonging to the other three groups by a high-fat diet followed by a streptozotocin (STZ) injection. The T2DM rats were further divided into a T2DM control group (DC), which was fed with the normal diet containing 50% common wheat flour, a high dose SGW group (HGW) fed with a diet containing 50% SGW flour, and a low dose SGW group (LGW) fed with a diet containing 25% SGW flour and 25% common wheat flour. Our results showed that SGW contained cereal antioxidants, particularly high in flavonoids and anthocyanins (46.14 ± 1.80 mg GAE/100 g DW and 1.73 ± 0.14 mg CGE/100 g DW, respectively). Furthermore, SGW exhibited a strong antioxidant activity in vitro (30.33 ± 2.66 μg TE/g DW, p < 0.01). Administration of the SGW at a high and low dose showed significant down-regulatory effects on fasting blood glucose (decreasing by 11.3% and 7.0%, respectively), insulin levels (decreasing by 12.3% and 9.7%, respectively), and lipid status (decreasing by 9.1% and 7.5%, respectively) in T2DM rats (p < 0.01). In addition, the T2DM groups treated with SGW at a high and low dose showed a significant increase in the blood superoxide dismutase (1.17 fold and 1.15 fold, respectively) and glutathione peroxidase activities (1.37 fold and 1.30 fold, respectively) compared with the DC group (p < 0.01). The normalized impaired antioxidant status of the pancreatic islet and of the liver compared with the DC group was also significantly increased. Our results indicated that SGW components exerting a glycemic control and a serum lipid regulation effect may be due to their free radical scavenging capacities to reduce the risk of T2DM in experimental diabetic rats.     

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 10¹⁰ CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1⁺ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.     

Dissociation between Corneal and Cardiometabolic Changes in Response to a Time-Restricted Feeding of a High Fat Diet

Mice fed a high fat diet (HFD) ab libitum show corneal dysregulation, as evidenced by decreased sensitivity and impaired wound healing. Time-restricted (TR) feeding can effectively mitigate the cardiometabolic effects of an HFD. To determine if TR feeding attenuates HFD-induced corneal dysregulation, this study evaluated 6-week-old C57BL/6 mice fed an ad libitum normal diet (ND), an ad libitum HFD, or a time-restricted (TR) HFD for 10 days. Corneal sensitivity was measured using a Cochet-Bonnet aesthesiometer. A corneal epithelial abrasion wound was created, and wound closure was monitored for 30 h. Neutrophil and platelet recruitment were assessed by immunofluorescence microscopy. TR HFD fed mice gained less weight (p < 0.0001), had less visceral fat (p = 0.015), and had reduced numbers of adipose tissue macrophages and T cells (p < 0.05) compared to ad libitum HFD fed mice. Corneal sensitivity was reduced in ad libitum HFD and TR HFD fed mice compared to ad libitum ND fed mice (p < 0.0001). Following epithelial abrasion, corneal wound closure was delayed (~6 h), and neutrophil and platelet recruitment was dysregulated similarly in ad libitum and TR HFD fed mice. TR HFD feeding appears to mitigate adipose tissue inflammation and adiposity, while the cornea remains sensitive to the pathologic effects of HFD feeding.     

Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance,Incretin Secretion and Appetite in Humans

Background: To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. Methods: Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At −30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. Results: PNO-FFA augmented GLP-1 secretion from 0–360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240–360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). Conclusions: In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.     

Curcumin Supplementation Ameliorates Bile Cholesterol Supersaturation in Hamsters by Modulating Gut Microbiota and Cholesterol Absorption

Curcumin is a polyphenol that has been shown to have prebiotic and cholesterol-lowering properties. This study aimed to investigate the impact of curcumin on bile cholesterol supersaturation and the potential mechanistic role of intestinal microbiota and cholesterol absorption. Male hamsters (n = 8) were fed a high-fat diet (HFD) supplemented with or without curcumin for 12 weeks. Results showed that curcumin significantly decreased cholesterol levels in the serum (from 5.10 to 4.10 mmol/L) and liver (from 64.60 to 47.72 nmol/mg protein) in HFD-fed hamsters and reduced the bile cholesterol saturation index (CSI) from 1.64 to 1.08 due to the beneficial modifications in the concentration of total bile acids (BAs), phospholipids and cholesterol (p < 0.05). Gut microbiota analysis via 16S rRNA sequencing revealed that curcumin modulated gut microbiota, predominantly increasing microbiota associated with BA metabolism and short-chain fatty acid production, which subsequently up-regulated the expression of hepatic cholesterol 7-alpha hydroxylase and increased the synthesis of bile acids (p < 0.05). Furthermore, curcumin significantly down-regulated the expression of intestinal Niemann–Pick C1-like protein 1(NPC1L1) in hamsters and reduced cholesterol absorption in Caco-2 cells (p < 0.05). Our results demonstrate that dietary curcumin has the potential to prevent bile cholesterol supersaturation through modulating the gut microbiota and inhibiting intestinal cholesterol absorption.     

GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6–8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.     

Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-¹³C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.     

The Combination of Berberine,Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.     

Protective Effect of Vanillic Acid against Hyperinsulinemia,Hyperglycemia and Hyperlipidemia via Alleviating Hepatic Insulin Resistance and Inflammation in High-Fat Diet (HFD)-Fed Rats

Excess free fatty acid accumulation from abnormal lipid metabolism results in the insulin resistance in peripheral cells, subsequently causing hyperinsulinemia, hyperglycemia and/or hyperlipidemia in diabetes mellitus (DM) patients. Herein, we investigated the effect of phenolic acids on glucose uptake in an insulin-resistant cell-culture model and on hepatic insulin resistance and inflammation in rats fed a high-fat diet (HFD). The results show that vanillic acid (VA) demonstrated the highest glucose uptake ability among all tested phenolic acids in insulin-resistant FL83B mouse hepatocytes. Furthermore, rats fed HFD for 16 weeks were orally administered with VA daily (30 mg/kg body weight) at weeks 13–16. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p < 0.05), indicating the protective effects of VA against hyperinsulinemia, hyperglycemia and hyperlipidemia in HFD rats. Moreover, VA significantly reduced values of area under the curve for glucose (AUC_glucose) in oral glucose tolerance test and homeostasis model assessment-insulin resistance (HOMA-IR) index, suggesting the improving effect on glucose tolerance and insulin resistance in HFD rats. The Western blot analysis revealed that VA significantly up-regulated expression of hepatic insulin-signaling and lipid metabolism-related protein, including insulin receptor, phosphatidylinositol-3 kinase, glucose transporter 2, and phosphorylated acetyl CoA carboxylase in HFD rats. VA also significantly down-regulated hepatic inflammation-related proteins, including cyclooxygenase-2 and monocyte chemoattractant protein-1 expressions in HFD rats. These results indicate that VA might ameliorate insulin resistance via improving hepatic insulin signaling and alleviating inflammation pathways in HFD rats. These findings also suggest the potential of VA in preventing the progression of DM.     

Association between Geriatric Nutrition Risk Index and The Presence of Sarcopenia in People with Type 2 Diabetes Mellitus: A Cross-Sectional Study

The aim of this cross-sectional study was to examine the association between the geriatric nutritional risk index (GNRI) and the prevalence of sarcopenia in people with type 2 diabetes (T2DM). Having both low handgrip strength (<28 kg for men and <18 kg for women) and low skeletal muscle mass index (<7.0 kg/m² for men and <5.7 kg/m² for women) was diagnosed as sarcopenia. GNRI was estimated by the formula as below: GNRI = (1.489 × serum albumin level [g/L]) + (41.7 × [current body weight (kg)/ideal body weight (kg)]). Participants were dichotomized on the basis of their GNRI scores (GNRI < 98, low; or GNRI ≥ 98, high). Among 526 people (301 men and 225 women) with T2DM, the proportions of participants with sarcopenia and low GNRI were 12.7% (n = 67/526) and 5.1% (n = 27/526), respectively. The proportion of sarcopenia in participants with low-GNRI was higher than that with high GNRI (44.4% [n = 12/27] vs. 11.0% [n = 55/499], p < 0.001). The GNRI showed positive correlations with handgrip strength (r = 0.232, p < 0.001) and skeletal muscle mass index (r = 0.514, p < 0.001). Moreover, low GNRI was related to the prevalence of sarcopenia (adjusted odds ratio, 4.88 [95% confidence interval: 1.88–12.7], p = 0.001). The GNRI, as a continuous variable, was also related to the prevalence of sarcopenia (adjusted odds ratio, 0.89 [95% confidence interval: 0.86–0.93], p < 0.001). The present study revealed that low GNRI was related to the prevalence of sarcopenia.     

A High-Dose Shiitake Mushroom Increases Hepatic Accumulation of Triacylglycerol in Rats Fed a High-Fat Diet: Underlying Mechanism

Shiitake mushroom have been shown to have health benefits including lowering plasma lipids and preventing body weight gain. However, their underlying mechanisms are largely unknown. The study aim was to assess the potential underlying mechanism of Shiitake mushrooms in lowering plasma triacylglycerol (TAG) in rats fed a high fat diet (HFD). Forty Wistar rats were divided into control group were given HFD and treatment group were fed HFD, enriched with Shiitake mushroom powder at a low dose (LD-M): 0.7%, medium dose (MD-M): 2%, or high dose (HD-M): 6% (wt:wt) for six weeks. Diets were isocaloric containing ~50% energy from fat. After six weeks’ dietary intervention, the rats were sacrificed, and blood and tissue samples were collected. The HD-M group showed a significantly higher ratio of liver weight to 100 g body weight (p < 0.05), a more severe hepatic steatosis marker, such as hepatocyte ballooning (p < 0.0001), and more liver triacylglycerol content than LD-M and MD-M (p < 0.05). HD-M also showed a significantly decreased ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) compared to HFD (p < 0.05), however, there were no differences compared to HD-M and MD-M. Our results also showed a positive association between the dosage, liver TAG, and liver ballooning histology. A negative association was found between the mushroom dosage and the ratio of liver PC to PE. This study showed the mechanism of how high-dose Shiitake mushroom (HD-M) prevents obesity by increasing TAG accumulation in the liver, rather than adipose tissue.     

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-β levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.