To investigate the functional effects of probiotic treatment on the gut microbiota, as well as liver and adipose gene expression in diet-induced obese mice.
Male C57BL/6J mice were fed a high-fat ...diet (HFD) for 8 weeks to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, n = 9) or HFD+placebo (n = 9) for another 10 weeks. Normal diet (ND) fed mice (n = 9) served as non-obese controls.
Diet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin, leptin, total-cholesterol and liver toxicity biomarkers. A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564, 5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups, respectively. Gut microbiota species were shared among the experimental groups despite the different diets and treatments. The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment. We observed concurrent transcriptional changes in adipose tissue and the liver. In adipose tissue, pro-inflammatory genes (TNFα, IL6, IL1β and MCP1) were down-regulated in mice receiving probiotic treatment. In the liver, fatty acid oxidation-related genes (PGC1α, CPT1, CPT2 and ACOX1) were up-regulated in mice receiving probiotic treatment.
The gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment. Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Worldwide estimates predict 2 billion people will be aged over 65 years by 2050. A major current challenge is maintaining mobility and quality of life into old age. Impaired mobility is often a ...precursor of functional decline, disability and loss of independence. Sarcopenia which represents the age-related decline in muscle mass is a well-established factor associated with mobility limitations in older adults. However, there is now evidence that not only changes in muscle mass but other factors underpinning muscle quality including composition, metabolism, aerobic capacity, insulin resistance, fat infiltration, fibrosis and neural activation may also play a role in the decline in muscle function and impaired mobility associated with ageing. Importantly, changes in muscle quality may precede loss of muscle mass and therefore provide new opportunities for the assessment of muscle quality particularly in middle-aged adults who could benefit from interventions to improve muscle function. This review will discuss the accumulating evidence that in addition to muscle mass, factors underpinning muscle quality influence muscle function and mobility with age. Further development of tools to assess muscle quality in community settings is needed. Preventative diet, exercise or treatment interventions particularly in middle-aged adults at the low end of the spectrum of muscle function may help preserve mobility in later years and improve healthspan.
Epidemiological evidence shows that consumption of dairy products is associated with decreased prevalence of metabolic related disorders, whilst evidence from experimental studies points towards ...dairy protein as a dietary component which may aid prevention of type 2 diabetes (T2DM). Poor metabolic health is a common characteristic of overweight, obesity and aging, and is the forerunner of T2DM and cardiovascular disease (CVD), and an ever increasing global health issue. Progressive loss of metabolic control is evident from a blunting of carbohydrate, fat and protein metabolism, which is commonly manifested through decreased insulin sensitivity, inadequate glucose and lipid control, accompanied by a pro-inflammatory environment and hypertension. Adverse physiological changes such as excess visceral adipose tissue deposition and expansion, lipid overspill and infiltration into liver, muscle and other organs, and sarcopaenia or degenerative loss of skeletal muscle mass and function all underpin this adverse profile. 'Sarcobesity' and sarcopaenic diabetes are rapidly growing health issues. As well as through direct mechanisms, dairy protein may indirectly improve metabolic health by aiding loss of body weight and fat mass through enhanced satiety, whilst promoting skeletal muscle growth and function through anabolic effects of dairy protein-derived branch chain amino acids (BCAAs). BCAAs enhance muscle protein synthesis, lean body mass and skeletal muscle metabolic function. The composition and processing of dairy protein has an impact on digestion, absorption, BCAA kinetics and function, hence the optimisation of dairy protein composition through selection and combination of specific protein components in milk may provide a way to maximize benefits for metabolic health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical ...utility, the field of pharmacoepigenomics has emerged to tackle the so-called “missing heritability” of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes. The majority of published studies have assessed the influence of antipsychotics on methylation levels in specific neurotransmitter-associated candidate genes or at the genome-wide level. While these studies illustrate the epigenetic modifications associated with antipsychotics, very few have assessed clinical outcomes and the potential of differential DNA methylation profiles as predictors of antipsychotic response. Results from other psychiatric disorder studies, such as depression and bipolar disorder, provide insight into what may be achieved by schizophrenia pharmacoepigenomics. Other aspects that should be addressed in future research include methodological challenges, such as tissue specificity, and the influence of genetic variation on differential methylation patterns.
•Antipsychotics both act upon and are influenced by DNA methylation in schizophrenia.•Studies have focused on the serotonergic, dopaminergic, and GABAergic systems.•Many complex factors, including genetic variation, influence DNA methylation.•DNA methylation shows promise as an antipsychotic response biomarker.•Recommended epigenetic studies could point to targets for epidrug development.
Scope: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be ...effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism.
Methods and results: LDLR−/− mice were fed a high‐cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM‐1 and VCAM‐1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A‐I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG‐CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment.
Conclusion: Long‐term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti‐atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.
Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully ...understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity.
C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2-4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages.
In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of diet-induced obesity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older ...adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.
The differential ability of various milk protein fractions to stimulate muscle protein synthesis (MPS) has been previously described, with whey protein generally considered to be superior to other ...fractions. However, the relative ability of a whole milk protein to stimulate MPS has not been compared to whey. Sixteen healthy middle-aged males ingested either 20 g of milk protein (n = 8) or whey protein (n = 8) while undergoing a primed constant infusion of ring (13)C₆ phenylalanine. Muscle biopsies were obtained 120 min prior to consumption of the protein and 90 and 210 min afterwards. Resting myofibrillar fractional synthetic rates (FSR) were 0.019% ± 0.009% and 0.021% ± 0.018% h(-1) in the milk and whey groups respectively. For the first 90 min after protein ingestion the FSR increased (p < 0.001) to 0.057% ± 0.018% and 0.052% ± 0.024% h(-1) in the milk and whey groups respectively with no difference between groups (p = 0.810). FSR returned to baseline in both groups between 90 and 210 min after protein ingestion. Despite evidence of increased rate of digestion and leucine availability following the ingestion of whey protein, there was similar activation of MPS in middle-aged men with either 20 g of milk protein or whey protein.
This study investigated the hepatoprotective effects of low doses of curcumin against liver damage induced by chronic alcohol intake and a high-fat diet. We also examined several potential underlying ...mechanisms including action on alcohol metabolism, antioxidant activity, AMPK level and lipid metabolism.
Alcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6weeks to mice fed a high-fat diet with or without two different doses of curcumin (0.02% and 0.05%, wt/wt).
Curcumin significantly decreased the plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities (p<0.05) and prevented hepatic steatosis compared with the alcohol control group. Curcumin significantly reversed the alcohol-induced inhibition of the alcohol dehydrogenase, aldehyde dehydrogenase 2 and antioxidant enzyme activities as well as the activation of cytochrome P4502E1 and promotion of lipid peroxidation (p<0.05). Curcumin significantly increased the hepatic total AMPK protein level and concomitantly suppressed the fatty acid synthase and phosphatidate phosphohydrolase activities compared with the alcohol control group (p<0.05). Furthermore, curcumin significantly lowered the plasma leptin, free fatty acids and triglycerides levels and hepatic lipid levels (p<0.05).
These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.
Bioelectrical impedance devices, however, typically have a day-to-day reliability of 2-4%. ...the differences in percentage body fat observed in the commuters using active or public transport are ...arguably well within the bounds of technical and biological variability in bioelectrical impedance analyses and hence of little clinical significance.
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