Showing papers on "Normal diet published in 2014"

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Abstract: Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6 months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.

Archaea and the human gut: New beginning of an old story

Abstract: Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics.

Diet and Exercise Orthogonally Alter the Gut Microbiome and Reveal Independent Associations With Anxiety and Cognition

Abstract: Background: The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise. Results: We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition. Conclusions: Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy.

Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation

Abstract: Insulin signaling in osteoblasts has been shown recently to contribute to whole-body glucose homeostasis in animals fed a normal diet; however, it is unknown whether bone contributes to the insulin resistance that develops in animals challenged by a high-fat diet (HFD). Here, we evaluated the consequences of osteoblast-specific overexpression of or loss of insulin receptor in HFD-fed mice. We determined that the severity of glucose intolerance and insulin resistance that mice develop when fed a HFD is in part a consequence of osteoblast-dependent insulin resistance. Insulin resistance in osteoblasts led to a decrease in circulating levels of the active form of osteocalcin, thereby decreasing insulin sensitivity in skeletal muscle. Insulin resistance developed in osteoblasts as the result of increased levels of free saturated fatty acids, which promote insulin receptor ubiquitination and subsequent degradation. Together, these results underscore the involvement of bone, among other tissues, in the disruption of whole-body glucose homeostasis resulting from a HFD and the involvement of insulin and osteocalcin cross-talk in glucose intolerance. Furthermore, our data indicate that insulin resistance develops in bone as the result of lipotoxicity-associated loss of insulin receptors.

Prevalence of Vitamin A Deficiency in South Asia: Causes, Outcomes, and Possible Remedies

Abstract: Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot’s spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD Children need additional vitamin A because they do not consume enough in their normal diet There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women Therefore, stern efforts are needed to address this issue of publichealth significance at local and international level in lower- and middle-income countries of South Asia

Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice

Abstract: Obesity is associated with metabolic disorders. Sulforaphane, an isothiocyanate, inhibits adipogenesis and the occurrence of cardiovascular disease. In this study, we investigated whether sulforaphane could prevent high-fat diet (HFD)-induced obesity in C57BL/6N mice. Mice were fed a normal diet (ND), HFD or HFD plus 0.1% sulforaphane (SFN) for 6 weeks. Food efficiency ratios and body weight were lower in HFD-SFN-fed mice than in HFD-fed mice. SFN attenuated HFD-induced visceral adiposity, adipocyte hypertrophy and fat accumulation in the liver. Serum total cholesterol and leptin, and liver triglyceride levels were lower in HFD-SFN-fed mice than in HFD-fed mice. SFN decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and leptin in the adipose tissue of HFD-SFN mice and increased adiponectin expression. Phosphorylation of AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase in the adipose tissue of HFD-SFN-fed mice was elevated, and HMG-CoA reductase expression was decreased compared with HFD-fed mice. Thus, these results suggest that SFN may induce antiobesity activity by inhibiting adipogenesis through down-regulation of PPARγ and C/EBPα and by suppressing lipogenesis through activation of the AMPK pathway.

Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway

Abstract: Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha-lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP-activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP-activated protein kinase pathway, the translocation of sterol regulatory element-binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2.

Enhanced recovery after surgery vs conventional care in emergency colorectal surgery.

Abstract: AIM: To investigate the feasibility and beneficial effects of enhanced recovery after surgery (ERAS) programme in the setting of emergency colorectal surgery. METHODS: Between January 2011 and October 2013, patients undergoing emergency resection for obstructing colorectal cancer at the Faculty of Medicine Siriraj Hospital, Bangkok, Thailand using ERAS programme were compared with those using conventional care (1:2 ratio). They were matched for their age, gender, ColoRectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity score, and type of surgery. Primary outcomes were length of hospital stay and postoperative morbidity. Secondary outcomes included gastrointestinal recovery, 30-d readmission, and time interval from surgery to chemotherapy. RESULTS: Twenty patients treated with ERAS programme were compared with 40 patients receiving conventional postoperative care. Median of hospital stay was shorter in the ERAS group: 5.5 d (range: 3-16) vs 7.5 d (range: 5-25), P = 0.009. The ERAS group had a non-significant reduction in the incidence of postoperative complication (25% vs 48%, P = 0.094). No 30-d mortality and readmission occurred. Patients with ERAS programme had a shorter time to first flatus (1.6 d vs 2.8 d, P < 0.001) and time to resumption of normal diet (3.5 d vs 5.5 d, P = 0.002). Time interval between operation and initiation of adjuvant chemotherapy was significantly shorter in the ERAS group (37 d vs 49 d, P = 0.009). CONCLUSION: The ERAS programme in the setting of emergency colorectal surgery was safe and feasible. It achieved significantly shorter hospitalisation and faster recovery of bowel function.

The effect of weight reduction on treatment outcomes in obese patients with psoriasis on biologic therapy: a randomized controlled prospective trial.

Abstract: Background: Obesity has long been associated with psoriasis and it is considered to be an independent risk factor for chronic heart diseases in these patients. Recently, some of the biologic drugs used for psoriasis have been reported to cause increase in body weight. It is currently not clear if this increased body weight seen in psoriasis patients on biologics leads to decrease in there efficacy or vice versa. We carried out this study to see if reduction in body weight leads to increased efficacy of biologics in obese psoriasis patients. Objective: To evaluate the effect of weight reduction by dietary control on treatment efficacy of biologics in obese patients as indicated by the Psoriasis Area and Severity Index (PASI) score. Methods: Obese patients with psoriasis receiving biologic therapy, satisfying the inclusion criterion, were randomized in a 1:1 ratio to receive low-calorie diet versus normal diet (control group). We included 262 patients with moderate to severe, stable plaque psoriasis with a ...

Nicotine improves obesity and hepatic steatosis and ER stress in diet-induced obese male rats.

Abstract: Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

High Fat Diet Exacerbates Neuroinflammation in an Animal Model of Multiple Sclerosis by Activation of the Renin Angiotensin System

Abstract: Epidemiological studies suggest a positive correlation between the incidence and severity of multiple sclerosis (MS) and the intake of fatty acids. It remains to be clarified whether high fat diet (HFD) indeed can exacerbate the disease pathology associated with MS and what the underlying mechanisms are. In this study, we determined the influence of HFD on the severity and pathology of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Mice were fed either normal diet (ND) or HFD and subsequently induced with EAE. Immunohistochemical staining and real-time PCR were used to determine immune cell infiltration and inflammatory mediators in the central nervous system (CNS). Our data show that HFD increases immune cell infiltration and inflammatory mediator production in the CNS and thereby aggravates EAE. Moreover, our data demonstrate that activation of the renin angiotensin system (RAS) is associated with the HFD-mediated effects on EAE severity. These results show that HFD exacerbates an autoreactive immune response within the CNS. This indicates that diets containing excess fat have a significant influence on neuroinflammation in EAE, which may have important implications for the treatment and prevention of neuroinflammatory disorders.

Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis.

Abstract: Vitamin B deficiencies, which can lead to hyperhomocysteinemia (Hhcy), are commonly reported in patients with inflammatory bowel disease (IBD) and may be a causative underlying factor. However, the mechanism for this effect is not known. Hydrogen sulfide (H2S) is a gaseous mediator that promotes tissue repair and resolution of inflammation. In experimental colitis, a marked increase in colonic H2S synthesis drives ulcer healing and resolution of inflammation. Because H2S synthesis is in part dependent upon enzymes that require vitamin B6 as a cofactor, we tested the hypothesis that Hhcy in rodent models would increase the susceptibility to colitis. In all three models tested, diet-induced Hhcy significantly exacerbated colitis. The usual elevation of colonic H2S synthesis after induction of colitis was absent in all three models of colitis. Administration of an H2S donor to Hhcy rats significantly decreased the severity of colitis. Compared with wild-type mice, interleukin (IL) 10-deficient mice on a normal diet had decreased levels of colonic H2S synthesis, a 40% increase in serum homocysteine, and a phenotype similar to wild-type mice with Hhcy. IL-10–deficient mice fed the vitamin B-deficient diet exhibited more severe colonic inflammation, but the normal elevation of colonic H2S synthesis was absent. Administration of IL-10 to the IL-10–deficient mice restored colonic H2S synthesis and significantly decreased serum homocysteine levels. These results suggest that the exacerbation of colitis in Hhcy is due in part to impaired colonic H2S synthesis. Moreover, IL-10 plays a novel role in promoting H2S production and homocysteine metabolism, which may have therapeutic value in conditions characterized by Hhcy.

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function

Abstract: Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death.

Lactobacillus plantarum NCU116 improves liver function, oxidative stress and lipid metabolism in rats with high fat diet induced non-alcoholic fatty liver disease

Abstract: The effect of Lactobacillus plantarum NCU116 on liver function, oxidative stress and lipid metabolism in rats with high fat diet induced non-alcoholic fatty liver disease (NAFLD) was studied. The rats were divided into four groups: the normal diet (ND) group; the high fat diet (HFD) group; and HFD plus L. plantarum NCU116 as two doses (NCU116-L, 108 CFU mL−1; NCU116-H, 109 CFU mL−1) groups. Treatment of L. plantarum NCU116 for 5 weeks was found to restore liver function and oxidative stress in rats with NAFLD, and decrease the levels of fat accumulation in the liver. In addition, the bacterium significantly reduced endotoxin and proinflammatory cytokines, and regulated bacterial flora in the colon and the expression of lipid metabolism in the liver. These results suggest that possible underlying mechanisms for the beneficial effect of L. plantarum NCU116 on NAFLD may include two pathways of downregulating lipogenesis and upregulating lipolysis and fatty acid oxidation related gene expression.

Overweight and CpG methylation of the Pomc promoter in offspring of high-fat-diet-fed dams are not “reprogrammed” by regular chow diet in rats

Abstract: This study aimed to determine whether epigenetic malprogramming induced by high-fat diet (HFD) has an obesogenic effect on nonmated and mated female rats and their offspring. Further, it aimed to reprogram offspring's epigenetic malprogramming and phenotype by providing normal diet after weaning. Body weight (BW) was measured, and plasma and hypothalamic arcuate nuclei were collected for analysis of hormones, mRNA, and DNA CpG methylation of the promoter of Pomc, a key factor in control of food intake. In nonmated females, HFD decreased Pomc/leptin ratio by ∼38%. This finding was associated with Pomc promoter hypermethylation. While heavier during pregnancy, during lactation HFD dams showed sharper BW decrease (2.5-fold) and loss of Pomc promoter hypermethylation. Moreover, their weight loss was correlated with demethylation (r=-0.707) and with gadd45b mRNA expression levels (r=0.905). Even though offspring of HFD dams ate standard chow from weaning, they displayed increased BW, Pomc promoter hypermethylation, and vulnerability to HFD challenge (3-fold kilocalorie intake increase). These findings demonstrate a long-term effect of maternal HFD on CpG methylation of the Pomc promoter in the offspring, which was not reprogrammed by standard chow from weaning. Further, the results suggest a possible mechanism of demethylation of the Pomc promoter following pregnancy and lactation.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

Abstract: Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload.

Defective insulin secretory response to intravenous glucose in C57Bl/6J compared to C57Bl/6N mice.

Abstract: Objective The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, recent reports comparing Bl/6J to Bl/6N (carrying the wild-type Nnt allele) under normal diet have led to conflicting results using glucose tolerance tests. Thus, we assessed glucose-stimulated insulin secretion (GSIS), insulin sensitivity, clearance and central glucose-induced insulin secretion in Bl/6J and N mice using gold-standard methodologies. Methods GSIS was measured using complementary tests (oral and intravenous glucose tolerance tests) and hyperglycemic clamps. Whole-body insulin sensitivity was assessed using euglycemic-hyperinsulinemic clamps. Neurally-mediated insulin secretion was measured during central hyperglycemia. Results Bl/6J mice have impaired GSIS compared to Bl/6N when glucose is administered intravenously during both a tolerance test and hyperglycemic clamp, but not in response to oral glucose. First and second phases of GSIS are altered without changes in whole body insulin sensitivity, insulin clearance, beta-cell mass or central response to glucose, thereby demonstrating defective beta-cell function in Bl/6J mice. Conclusions The Bl/6J mouse strain displays impaired insulin secretion. These results have important implications for choosing the appropriate test to assess beta-cell function and background strain in genetically modified mouse models.

Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats.

Abstract: Background Obese-insulin resistance caused by long-term high-fat diet (HFD) consumption is associated with left ventricular (LV) dysfunction and increased risk of myocardial infarction. Metformin and vildagliptin have been shown to exert cardioprotective effects. However, the effect of these drugs on the hearts under obese-insulin resistance with ischemia-reperfusion (I/R) injury is unclear. We hypothesized that combined vildagliptin and metformin provide better protective effects against I/R injury than monotherapy in obese-insulin resistant rats. Methodology Male Wistar rats were fed either HFD or normal diet. Rats in each diet group were divided into 4 subgroups to receive vildagliptin, metformin, combined vildagliptin and metformin, or saline for 21 days. Ischemia due to left anterior descending artery ligation was allowed for 30-min, followed by 120-min reperfusion. Metabolic parameters, heart rate variability (HRV), LV function, infarct size, mitochondrial function, calcium transient, Bax and Bcl-2, and Connexin 43 (Cx43) were determined. Rats developed insulin resistance after 12 weeks of HFD consumption. Vildagliptin, metformin, and combined drugs improved metabolic parameters, HRV, and LV function. During I/R, all treatments improved LV function, reduced infarct size and Bax, increased Bcl-2, and improved mitochondrial function in HFD rats. However, only combined drugs delayed the time to the first VT/VF onset, reduced arrhythmia score and mortality rate, and increased p-Cx43 in HFD rats. Conclusion Although both vildagliptin and metformin improved insulin resistance and attenuate myocardial injury caused by I/R, combined drugs provided better outcomes than single therapy by reducing arrhythmia score and mortality rate.

Antioxidant Effects of Spinach (Spinacia oleracea L.) Supplementation in Hyperlipidemic Rats

Abstract: Increased consumption of fresh vegetables that are high in polyphenols has been associated with a reduced risk of oxidative stress-induced disease. The present study aimed to evaluate the antioxidant effects of spinach in vitro and in vivo in hyperlipidemic rats. For measurement of in vitro antioxidant activity, spinach was subjected to hot water extraction (WE) or ethanol extraction (EE) and examined for total polyphenol content (TPC), oxygen radical absorbance capacity (ORAC), cellular antioxidant activity (CAA), and antigenotoxic activity. The in vivo antioxidant activity of spinach was assessed using blood and liver lipid profiles and antioxidant status in rats fed a high fat-cholesterol diet (HFCD) for 6 weeks. The TPC of WE and EE were shown as 1.5±0.0 and 0.5±0.0 mg GAE/g, respectively. Increasing the concentration of the extracts resulted in increased ORAC value, CAA, and antigenotoxic activity for all extracts tested. HFCD-fed rats displayed hyperlipidemia and increased oxidative stress, as indicated by a significant rise in blood and liver lipid profiles, an increase in plasma conjugated diene concentration, an increase in liver thiobarbituric acid reactive substances (TBARS) level, and a significant decrease in manganese superoxide dismutase (Mn-SOD) activity compared with rats fed normal diet. However, administration of 5% spinach showed a beneficial effect in HFCD rats, as indicated by decreased liver TBARS level and DNA damage in leukocyte and increased plasma conjugated dienes and Mn-SOD activity. Thus, the antioxidant activity of spinach may be an effective way to ameliorate high fat and cholesterol diet-induced oxidative stress.

T cell costimulation protects obesity-induced adipose inflammation and insulin resistance

Abstract: A key pathophysiologic role for activated T-cells in mediating adipose inflammation and insulin resistance (IR) has been recently postulated. However, mechanisms underlying their activation are poorly understood. In this study, we demonstrated a previously unrecognized homeostatic role for the costimulatory B7 molecules (CD80 and CD86) in preventing adipose inflammation. Instead of promoting inflammation, which was found in many other disease conditions, B7 costimulation reduced adipose inflammation by maintaining regulatory T-cell (Treg) numbers in adipose tissue. In both humans and mice, expression of CD80 and CD86 was negatively correlated with the degree of IR and adipose tissue macrophage infiltration. Decreased B7 expression in obesity appeared to directly impair Treg proliferation and function that lead to excessive proinflammatory macrophages and the development of IR. CD80/CD86 double knockout (B7 KO) mice had enhanced adipose macrophage inflammation and IR under both high-fat and normal diet conditions, accompanied by reduced Treg development and proliferation. Adoptive transfer of Tregs reversed IR and adipose inflammation in B7 KO mice. Our results suggest an essential role for B7 in maintaining Tregs and adipose homeostasis and may have important implications for therapies that target costimulation in type 2 diabetes.

Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle

Abstract: Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle. Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.