Shuyu Yang

Irisin is inversely associated with intrahepatic triglyceride contents in obese adults

BACKGROUND & AIMS Obesity is closely related to non-alcoholic fatty liver disease (NAFLD), which has become an important public health problem because of its high prevalence and association with metabolic syndromes. Irisin was recently identified as a novel peptide to improve obesity and glucose homeostasis, and considered to be therapeutic for human metabolic diseases. The aim of this study was to examine the association of serum irisin concentration and liver triglyceride contents in obese Chinese adults. METHODS Serum irisin levels were measured and liver fat contents determined by (1)H MRS in 296 obese adults. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose, and lipid profiles were detected. The liver triglyceride contents of subjects were measured by (1)H MRS. The protein levels of irisin were determined by quantitative ELISA. RESULTS We found that serum irisin levels were reduced in obese adults with NAFLD. By dividing the distribution of intrahepatic triglyceride (IHTG) contents into quartiles, serum irisin levels were reduced gradually with the increase of IHTG contents (p<0.01). Higher serum irisin levels were associated with preferable TG levels. Serum ALT and AST concentrations were inversely correlated with serum irisin levels. Multivariate linear regression analysis demonstrated that serum irisin levels were independently associated with liver fat (p<0.01). By logistic regression analysis, the odds ratio for higher IHTG contents was reduced by 12.4% per 1 SD increase in serum irisin concentrations after adjustment for multivariate metabolic factors [OR (95% CI); 0.876 (0.777-0.987)]. CONCLUSIONS These results demonstrated that serum irisin concentrations were inversely associated with the triglyceride contents in the liver and liver enzymes in obese Chinese adults.

Association of Serum Irisin with Metabolic Syndrome in Obese Chinese Adults

Irisin, a recently identified novel myokine, drives brown-fat-like conversion of white adipose tissues and has been proposed to mediate beneficial effects of exercise on metabolism. Circulating irisin was significantly reduced in type 2 diabetes patients; however, no evidence is available about its association with metabolic syndrome (MetS) and effects of adiposity and muscle mass on circulating irisin have been controversial. Cross-sectional data on socio-demographic, lifestyle, clinical characteristics and serum irisin were collected for 1,115 community-living Chinese adults with central obesity. Associations of serum irisin with MetS (central obesity plus any two of the following four factors (raised blood pressure (BP), raised fasting plasma glucose (FPG), raised triglyceride (TG), and reduced HDL cholesterol) and each component of MetS were analyzed using multivariable logistic regression. Among the 1,115 obese Chinese adults with a mean age of 53.2(±7.2) years, serum irisin levels (log-transformed) were significantly reduced in subjects with MetS and raised FPG than their control groups (p = 0.034 and 0.041, respectively). After adjustment for potential confounders, serum irisin was significantly associated with reduced risks of MetS and raised FPG, with odds ratios (ORs) (95% CI) per standard deviation of log-transformed irisin of 0.796 (0.505–0.959, p = 0.027) and 0.873 (0.764–0.998, p = 0.046), respectively. Associations of irisin with raised BP, raised TG and reduced HDL were not statistically significant ((ORs) (95% CI): 0.733(0.454–1.182, p = 0.202), 0.954(0.838–1.086, p = 0.478) and 1.130(0.980–1.302, p = 0.092), respectively). Stepwise multivariable linear regression analysis showed that fasting insulin, HbA1c and albumin/globulin ratio were negatively associated with serum irisin level with statistical significance (all p-values <0.05) and waist circumference was negatively associated with serum risin with marginally statistical significance (p = 0.055). These results imply that irisin may play an important role in insulin resistance and MetS and should be confirmed in future prospective studies.

Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta‐analysis

Objectives  Insulin‐sensitizing drugs (ISDs) have been advocated for the long‐term treatment of polycystic ovary syndrome (PCOS). It is therefore important to compare the efficacy and safety of ISDs such as metformin and thiazolidinediones (TZDs) for the treatment of this syndrome.

Puerarin improves insulin resistance and modulates adipokine expression in rats fed a high-fat diet

The link between obesity and insulin resistance largely accounts for the pathogenesis of metabolic syndrome and diabetes mellitus, in which adipokine expression plays a key role. Puerarin, a major active isoflavone extracted from the traditional Chinese medicine Radix Puerariae, has been studied for its comprehensive biological actions. However, its effect on high-fat diet (HFD)-induced insulin resistance and adipokine expression in rat has not been well investigated. In the present study, male Sprague-Dawley rats were fed on a normal control diet (NCD) or HFD for 6 weeks, followed by administration of puerarin (100 and 200 mg/kg) for up to 8 weeks. Compared to NCD, HFD feeding for 6 weeks led to increased body weight gain and impaired glucose/insulin tolerance manifested by oral glucose/intraperitoneal insulin tolerance tests in rats. These exacerbations prolonged through HFD feeding, but were effectively reversed by puerarin administration. Enzyme-linked immunosorbent assay demonstrated that, serum levels of leptin and resistin, but not that of adiponectin, were markedly augmented by HFD and retarded by puerarin treatment. Real-time reverse transcription polymerase chain reaction results showed that, in agreement with the circulating levels, mRNA expression of leptin and resistin in epididymal white adipose tissue was modified by HFD and improved by puerarin in the same pattern. Collectively, we revealed that puerarin could improve body weight gain, glucose/insulin intolerance and adipokine expression in HFD-induced insulin resistant rats, indicating its potential value for treatment of metabolic syndrome.

Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial

IMPORTANCE Nonalcoholic fatty liver disease (NAFLD) is a prevalent risk factor for chronic liver disease and cardiovascular disease. OBJECTIVE To compare the effects of moderate and vigorous exercise on intrahepatic triglyceride content and metabolic risk factors among patients with NAFLD. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, participants with central obesity and NAFLD were recruited from community-based screening in Xiamen, China, from December 1, 2011, through December 25, 2013. Data analysis was performed from August 28, 2015, through December 15, 2015. INTERVENTIONS Participants were randomly assigned to vigorous-moderate exercise (jogging 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months), moderate exercise (brisk walking 150 minutes per week for 12 months), or no exercise. MAIN OUTCOMES AND MEASURES Primary outcome, change in intrahepatic triglyceride content measured by proton magnetic resonance spectroscopy at 6 and 12 months; secondary outcomes, changes in body weight, waist circumference, body fat, and metabolic risk factors. RESULTS A total of 220 individuals (mean [SD] age, 53.9 [7.1] years; 149 woman [67.7%]) were randomly assigned to control (n = 74), moderate exercise (n = 73), and vigorous-moderate exercise (n = 73) groups. Of them, 211 (95.9%) completed the 6-month follow-up visit; 208 (94.5%) completed the 12-month follow-up visit. Intrahepatic triglyceride content was reduced by 5.0% (95% CI, -7.2% to 2.8%; P < .001) in the vigorous-moderate exercise group and 4.2% (95% CI, -6.3% to -2.0%; P < .001) in the moderate exercise group compared with the control group at the 6-month assessment. It was reduced by 3.9% (95% CI, -6.0% to -1.7%; P < .001) in the vigorous-moderate exercise group and 3.5% (95% CI, -5.6% to -1.3%; P = .002) in the moderate exercise group compared with the control group at the 12-month assessment. Changes in intrahepatic triglyceride content were not significantly different between vigorous-moderate and moderate exercise at the 6- or 12-month assessment. Body weight, waist circumference, and blood pressure were significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 6-month assessment and in the vigorous-moderate and moderate exercise groups compared with the control group at the 12-month assessment. In addition, body fat was significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 12-month assessment. After adjusting for weight loss, the net changes in intrahepatic triglyceride content were diminished and became nonsignificant between the exercise and control groups (except for the moderate exercise group at the 6-month assessment). CONCLUSIONS AND RELEVANCE Vigorous and moderate exercise were equally effective in reducing intrahepatic triglyceride content; the effect appeared to be largely mediated by weight loss. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01418027.

Chinese Lacto-Vegetarian Diet Exerts Favorable Effects on Metabolic Parameters, Intima-Media Thickness, and Cardiovascular Risks in Healthy Men

BACKGROUND To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P<0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

Puerarin protects pancreatic β-cell survival via PI3K/Akt signaling pathway

Pancreatic β-cell loss because of apoptosis is the major cause of type 1 diabetes (T1D) and late stage T2D. Puerarin possesses anti-diabetic properties; whether it acts directly on pancreatic β-cell is not clear. This study was designed to investigate the effects of puerarin on pancreatic β-cell survival and function. Diabetes was induced in male C57BL/6 mice by a single peritoneal injection of streptozotocin (STZ). Pancreatic β-cell survival and function were assessed in diabetic mice by measuring β-cell apoptosis, β-cell mass, pancreatic insulin content, and glucose tolerance, and in cultured islets and clonial MIN6 β-cells by measuring β-cell viability and apoptosis and glucose-stimulated insulin secretion. We found that pre-treatment with puerarin decreased the incidence of STZ-induced diabetes. Puerarin increased pancreatic β-cell mass via β-cell apoptosis inhibition in diabetic mice, and increased serum insulin, whereas it decreased blood glucose levels and improved glucose tolerance. In cultured islets and MIN6 cells, puerarin protected β-cell from cobalt chloride (CoCl2)-induced apoptosis and restored the impaired capacity of glucose-stimulated insulin secretion. Puerarin protection of β-cell survival involved the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In conclusion, puerarin protects pancreatic β-cell function and survival via direct effects on β-cells, and its protection of β-cell survival is mediated by the PI3K/Akt pathway. As a safe natural plant extraction, puerarin might serve as a preventive and/or therapeutic approach for diabetes.

Relationship of carotid intima-media thickness and duration of vegetarian diet in Chinese male vegetarians.

ObjectiveMany studies have shown that vegetarian diet has beneficial effects on the prevention of cardiovascular diseases. However, the effect of vegetarian diet on carotid intima-media thickness (IMT), as well as the association between IMT and duration of vegetarian diet, are still unclear. The present study aims to investigate the influence of duration of vegetarian diet on cardiovascular risk factors, and more importantly on IMT among Chinese vegetarians.MethodsOne hundred and seventy-one Chinese male vegetarians were screened for metabolic profile, cardiovascular risk and carotid IMT. They were compared with 129 age-matched omnivores recruited from a community-based health project. The effects of confounding factors were adjusted by stepwise logistic regression analysis.ResultsCompared to the omnivores, the vegetarians had lower BMI, weight, systolic blood pressure and diastolic blood pressure. Also, the levels of triglyceride, total cholesterol, HDL-Cholesterol, LDL-Cholesterol, ApoA1, ApoB, uric acid, albumin and γ-glutamyltransferase were significantly reduced in vegetarians. Omnivores had significantly higher fasting blood glucose than that of vegetarians. However, there were no differences in fasting insulin, C-reactive protein and HOMA-IR between the two groups. IMT was thinner in the vegetarian group than in the omnivore group (0.59 ± 0.16 vs. 0.63 ± 0.10 cm, P < 0.05). The vegetarians were divided according to duration of vegetarian diet (< 6 years, 6 to ≤ 11 years, > 11 years), those in tertile 1 (< 6 years) and tertile 2 (6 to ≤ 11 years) had shown thinner IMT as compared to the omnivores, and tertile 3 had shown no reduction.ConclusionA decrease in multiple cardiovascular risk factors such as BMI, blood pressure and lipid profile was associated with vegetarian diet. Moreover, taking a low-calorie, low-protein, or vegetarian diet might have great beneficial effects on IMT through improved lipid profile, and the beneficial effects appeared to be correlated with the duration of vegetarian diet.

An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy

Diabetic retinopathy (DR), in which inflammation has been implicated playing important roles, is one of the most common diabetes complications. Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis, is a classical prescription in Traditional Chinese Medicine for treating inflammation and ischemic diseases. Here, we investigated the effects of a modified recipe of DBT, with addition of Panax notoginseng, in treating diabetic retinopathy. An aqueous extract of Radix Astragali, Radix Angelica sinensis, and Panax notoginseng (RRP) was given to Goto-Kakizaki (GK) rats and streptozotocin-induced Sprague-Dawley (SD) rats. Leukostasis, vascular leakage, and acellular capillaries in retinal vasculature of animals were determined. Expression of retinal inflammatory biomarkers was assessed. We found that RRP reduced leukostasis, acellular capillaries, and vascular leakage compared to diabetic control rats. We also found that RRP decreased the expression of inflammatory factors including IL-1β, IL-6, TNF-α, NF-κB, MCP-1, ICAM-1, or VCAM-1 in the retinas of GK rats and reversed high glucose-induced inhibition of endothelial cell migration and proliferation in vitro. We conclude that RRP has a potent effect in preventing the pathogenesis and/or progression of DR and thus may serve as a promising nontoxic therapeutic approach of DR.