A combination of grape extract, green tea extract and L-carnitine improves high-fat diet-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease in mice

To develop a therapeutic agent for obesity-related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l-carnitine (RGTC), and its effects on obesity, hyperlipidemia and non-alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high-fat diet (HFD)-induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration-dependently suppressed the HFD-induced increase in plasma lipids, such as low-density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD-fed C57BL/6 mice. The plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were also significantly down-regulated by RGTC treatment. These results suggest that RGTC suppressed HFD-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders.     

Hepatoprotective Activity of Scutellariae Radix Extract in Mice Fed a High Fat Diet with Chronic Alcohol Exposure

Scutellariae radix (SR) is an herbal medicine used for the treatment of inflammatory diseases. To investigate whether the SR water extract has a hepatoprotective effect in mice fed a high fat diet with chronic alcohol consumption, ICR mice were fed one of the following diets: a control diet (CD, 16% fat), a high fat diet (HFD, 40% fat), a high fat diet with either ethanol (HFDE, 25% v/v, ad libitum) alone or ethanol with SR extract (HFDESR, 100 mg/kg, p.o.) for 28 days, respectively. The combination of high fat diet with ethanol exposure induced hepatic damage that was manifested by a significant increase in the activities of functional enzymes, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) in serum. Also, the liver and visceral fat weights were increased and the lipid profiles in serum and liver homogenate including triglyceride, total cholesterol, LDL‐cholesterol were significantly deteriorated. The SR supplements significantly reversed these altered parameters to near the values of the CD mice. Specifically, the expression of 3‐hydroxy‐3‐methylglutaryl‐coenzymeA (HMG‐CoA) reductase in liver homogenate was significantly lowered in the HFDESR group compared with that of either the HFD or HFDE groups, which revealed that the SR extract could afford protection in the alleviation of high fat and alcoholic liver damage. Copyright © 2011 John Wiley & Sons, Ltd.     

Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian Older Adult Cohort Study

OBJECTIVES: To describe associations between dietary nutrient intake and progression of sarcopenia, the age‐related loss of muscle mass and strength. DESIGN: Prospective cohort study of community‐dwelling older adults. SETTING: Southern Tasmania, Australia. PARTICIPANTS: Seven hundred forty noninstitutionalized older adults (50% female; mean age 62±7) randomly sampled from electoral rolls. MEASUREMENTS: Dietary nutrient intake was examined at baseline and follow‐up (2.6±0.4 years later) using The Cancer Council Victoria's Food Frequency Questionnaire (FFQ). Appendicular lean mass (aLM) was assessed using dual X‐ray absorptiometry and muscle strength of the knee extensors using a dynamometer. RESULTS: Failing to meet the recommended dietary intake for protein was associated with significantly lower aLM at baseline (?0.81 kg, 95% confidence interval (CI)=?1.54 to ?0.08) and follow‐up (?0.79 kg, 95%CI=?1.42 to ?0.17). Energy‐adjusted protein intake was a positive predictor of change in aLM over 2.6 years (β=0.10, P=.003). Energy‐adjusted intake of iron (β=0.07, P=.02), magnesium (β=0.07, P=.02), phosphorus (β=0.07, P=.047), and zinc (β=0.08, P=.02) were positive predictors of change in aLM, whereas retinol (β=?0.09, P=.005) was a negative predictor of change in aLM after adjustment for protein intake. No significant associations were observed between nutrient intake and muscle strength. CONCLUSION: Protein and several other dietary nutrients are associated with muscle mass and rate of muscle loss (but not strength) in older adults, suggesting that multiple dietary components may ameliorate the progression of sarcopenia.     

Reproductive axis function and gonadotropin microheterogeneity in a male rat model of diet-induced obesity

Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17β-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.     

Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene

A hallmark of diabetes is an absolute or relative reduction in the number of functional β cells. Therapies that could increase the number of endogenous β cells under diabetic conditions would be desirable. Prevalent gene targeting mouse models for assessing β-cell proliferation and diabetes pathogenesis only address whether deletion of a gene prevents the development of diabetes. Models testing whether acute excision of a single gene can ameliorate or reverse preexisting hyperglycemia in established diabetes remain to be explored, which could directly validate the effect of gene excision on treating diabetes. Here, we report that acute and temporally controlled excision of the Men1 gene, which encodes menin, ameliorated preexisting hyperglycemia in streptozotocin-treated mice. Moreover, Men1 excision also improved the preexisting hyperglycemia and glucose intolerance in genetic db/db diabetic mice. Furthermore, acute Men1 excision reversed preexisting glucose intolerance in high-fat diet-fed mice. Men1 excision improved glucose metabolism at least partly through increasing proliferation of endogenous β cells and islet size. Acute Men1 excision up-regulated a group of proproliferative genes in pancreatic islets. Together, these findings demonstrate that established hyperglycemia can be reversed through repression of a single gene, Men1, in diabetic conditions, and suggest that menin is a vital regulator in pathogenesis of diabetes.     

Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity

The neuronal circuits involved in the regulation of feeding behavior and energy expenditure are soft-wired, reflecting the relative activity of the postsynaptic neuronal system, including the anorexigenic proopiomelanocortin (POMC)-expressing cells of the arcuate nucleus. We analyzed the synaptic input organization of the melanocortin system in lean rats that were vulnerable (DIO) or resistant (DR) to diet-induced obesity. We found a distinct difference in the quantitative and qualitative synaptology of POMC cells between DIO and DR animals, with a significantly greater number of inhibitory inputs in the POMC neurons in DIO rats compared with DR rats. When exposed to a high-fat diet (HFD), the POMC cells of DIO animals lost synapses, whereas those of DR rats recruited connections. In both DIO rats and mice, the HFD-triggered loss of synapses on POMC neurons was associated with increased glial ensheathment of the POMC perikarya. The altered synaptic organization of HFD-fed animals promoted increased POMC tone and a decrease in the stimulatory connections onto the neighboring neuropeptide Y (NPY) cells. Exposure to HFD was associated with reactive gliosis, and this affected the structure of the blood-brain barrier such that the POMC and NPY cell bodies and dendrites became less accessible to blood vessels. Taken together, these data suggest that consumption of an HFD has a major impact on the cytoarchitecture of the arcuate nucleus in vulnerable subjects, with changes that might be irreversible due to reactive gliosis.     

Can Mediterranean diet really influence obesity? Evidence from propensity score matching

Worldwide obesity rates have stimulated interest in healthy dietary patterns. One well-known dietary pattern is the Mediterranean diet, which has been linked with several beneficial health effects. However, concerns have also been raised regarding the Mediterranean diet’s role in promoting weight gain. We explored the effect of the Mediterranean diet on body mass index using the propensity score matching approach. We found no statistically significant average treatment effect on the treated and therefore cannot confirm that a causal link exists between Mediterranean diet and body mass index.

低蛋白饮食对3/4期慢性肾脏病患者肾功能及营养状况的影响

Objective To assess the influences of low-protein diet on the renal function and nutritional status in patients with stage 3/4 chronic kidney diseases (CKD).Methods Totally 34 patients with stage 3/4 CKD were randomly divided into group A (protein intake:0.6 g·kg~(-1)·d~(-1);n=14) and B (protein intake:0.8 g·kg~(-1)·d~(-1);n=20).Anthropometric measurement and blood biochemical tests were performed,nutri-tional status was assessed,and 24-hour dietary recall survey was conducted before and after the treatment.Patients were followed up for 6 months.Results In group A,the creatinine level significantly decreased (P=0.010),while albumin level (P=0.042) and the intake of energy (P=0.018) and carbohydrate (P<0.001) signifi-cantly increased after the treatment In all the 34 patients,in group A and group B,the malnutrition rates were de-creased by 14.7%,7.2%,and 21.1% after nutritional intervention.Conclusion The low-protein diet (protein intake 0.6 g·kg~(-1)·d~(-1)),in which part of the staple food was replaced by wheat starch,can increase the in-takes of carbohydrate and energy and improve renal function and nutritional status in patients with stage 3/4 CKD.     

Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100

The in vivo pharmacokinetics/pharmacodynamics of 2′-O-(2-methoxyethyl) (2′-MOE) modified antisense oligonucleotides (ASOs), targeting apolipoprotein B-100 (apoB-100), were characterized in multiple species. The species-specific apoB antisense inhibitors demonstrated target apoB mRNA reduction in a drug concentration and time-dependent fashion in mice, monkeys, and humans. Consistent with the concentration-dependent decreases in liver apoB mRNA, reductions in serum apoB, and LDL-C, and total cholesterol were concurrently observed in animal models and humans. Additionally, the long duration of effect after cessation of dosing correlated well with the elimination half-life of 2′-MOE modified apoB ASOs studied in mice (t_1/2 ≅ 20 days) and humans (t_1/2 ≅ 30 days) following parental administrations. The plasma concentrations of ISIS 301012, observed in the terminal elimination phase of both mice and monkeys were in equilibrium with liver. The partition ratios between liver and plasma were similar, approximately 6000:1, across species, and thus provide a surrogate for tissue exposure in humans. Using an inhibitory E_max model, the ASO liver EC_50s were 101 ± 32, 119 ± 15, and 300 ± 191 μg/g of ASO in high-fat-fed (HF) mice, transgenic mice containing the human apoB transgene, and monkeys, respectively. The estimated liver EC₅₀ in man, extrapolated from trough plasma exposure, was 81 ± 122 μg/g. Therefore, extraordinary consistency of the exposure-response relationship for the apoB antisense inhibitor was observed across species, including human. The cross-species PK/PD relationships provide confidence in the use of pharmacology animal models to predict human dosing for second-generation ASOs targeting the liver.     

饮食习惯、体育锻炼及其交互作用对糖尿病发病的影响

目的探讨饮食习惯、体育锻炼以及两者的交互作用与糖尿病发病的相关性,为糖尿病预防和干预措施的制定提供科学依据。方法采用1：1配对病例对照设计,应用自行设计的问卷调查柳州市296对病例和对照的可能的糖尿病发病相关因素,并进行单因素和多因素条件Logistic回归分析。结果多因素条件Logistic回归分析显示,嗜甜食（OR=1666,P=0.000）、嗜高脂食品（OR=1.429,P=0.007）以及缺乏体育锻炼（OR=1.212,P=0.030）是糖尿病发病的独立危险因素;嗜甜食（P=0.792）及嗜成食（P=0.193）与体育锻炼无显著的相乘模型交互作用。结论少食甜食、成食以及经常参加体育锻炼有助于预防糖尿病。