Control High-fat Diet Research Articles

Role of macrophage polarization in lung injury in obese rats with acute necrotizing pancreatitis

Objective To investigate whether obesity aggravates acute lung injury and its mechanism in acute necrotizing pancreatitis. Methods Twenty-four male Sprague-Dawley rats were randomly divided into a normal diet control group (N-control), a normal diet-ANP group (N-ANP), and a high-fat diet control group (H-control), and a high fat diet-ANP group (H-ANP). Serum amylase (AMY), lipase (LIP), triglyceride (TG) and total cholesterol (TC) were determined by automatic biochemical analyzer. CD68, CD11c, CD206, toll like receptor-4 (TLR4), myeloperoxidase (MPO), interleukin (IL)-1β and nuclear factor-κB (NF-κB) in the lung tissue were detected by immunofluorescence or immunohistochemistry. The pancreas and lung tissues were observed under microscope and scored. SPSS 22.0 software was used. The data were expressed as mean±standard deviation. The t test, one-way ANOVA and SNK test were used. Results The TG and TC of the H-control group were (1.00±0.36) and (2.51±0.41) U/L, which were higher than those of the N-control group (0.53±0.19) and (1.72±0.52) U/L. The differences were statistically significant (t=-3.288, -3.062, P<0.05); AMY and LIP of the N-ANP group were (8 690.00±1 951.35), (9 650.00±1 810.19) U/L, which were higher than the N-control group (2 018.50±382.05), (90.26±7.00) U/L, the difference was statistically significant (q=9.452, 18.090, P<0.05); the LIP of the H-ANP group was (39 705.75±1 345.55) U/L, which was higher than the N-ANP group (q=59.940, P<0.05). The pancreas and lung scores in the N-ANP group were (11.40±1.80) and (6.62±1.06) points, which were higher than those in the N-control group (0.31±0.29) and (0.75±0.88). The difference was statistically significant (q=21.950, 17.160, P<0.05). The lung score of the H-ANP group was (8.19±1.07) points, which was higher than that of the N-ANP group (q=4.017, P<0.05), and the difference was statistically significant. The lung NF-κB of N-ANP group was (0.38±0.02), which was higher than that of N-control group (0.23±0.02) and lower than that of H-ANP group (0.48±0.01). The difference was statistically significant (q=21.830, 13.030, P<0.05). The number of IL-1β, MPO, CD68+ , CD68+ /CD11C+ , CD68+ /TLR4+ cells in the N-ANP group was (43.80±4.29), (105.81±5.37), (34.17±3.27), (13.32±1.83), (18.43±1.06), higher than the N-control group (4.93±1.13), (10.37±1.77), (20.16±2.42), (1.54±0.75), (8.37±1.40), the difference was statistically significant (q=29.530, 51.010, 15.261, 17.952, 20.965, P<0.05), lower than the H-ANP group (92.58±5.83), (175.71±8.85), (41.61±2.56), (16.92±1.96), (22.91±2.10), the difference was statistically significant (q=36.820, 37.100, 8.176, 8.079, 6.467, P<0.05). The number of lung CD68+ /CD206+ cells in the N-ANP group was (20.43±1.30), which was higher than that in the N-control group (11.65±1.51) and H-ANP group (14.83±1.83). The difference was statistically significant (q=16.613, 10.682, P<0.05). Conclusion Obesity can aggravate ALI in ANP, which may be related to the degree of activation of TLR4 signaling pathway in lung macrophages, leading to the polarization of macrophages to proinflammatory direction and release of more inflammatory mediators. Key words: Obesity; Acute necrotizing pancreatitis; Acute lung injury

Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization.

Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.

Antioxidant Properties of Saffron Stigma and Petals: A Potential Therapeutic Approach for Insulin Resistance through an Insulin-Sensitizing Adipocytokine in High-Calorie Diet Rats.

Background:Oxidative stress and alteration of lipid profile due to obesity and overweight is a major risk factor for atherosclerotic plaque or coronary artery disease. Because of antioxidant and lipid lowering potential of saffron, this study investigated weight alteration, lipid profiles, and insulin resistance index in high-calorie diet rats treated with aqueous extract of saffron stigma and petal.Methods:Forty Sprague-Dawley male rats were randomly divided into 8 groups including healthy control, high-fat diet control, nicotinic acid treated, Anethum graveolens treated, and saffron stigma and petal treated groups. Rats received a high-calorie diet for 16 weeks. For treatment, aqueous extract of saffron stigma (40 and 80 mg/kg) and petal (50 and 100 mg/kg) was used once daily for 4 weeks. Afterward, lipid profile, oxidative stress status, and insulin and adiponectin levels were measured using desired kits.Results:There was a significant decrease in the mean weight of the groups receiving saffron stigma and petal compared to control group (P < 0.05). The increased level of insulin hormone in obese group was improved in treated groups especially in the case of saffron stigma. Also, the decreased level of adiponectin was recovered in treated groups. An improvement was seen in oxidative stress markers and lipid profiles in treated groups compared to obesity pair.Conclusions:In this study, a remarkable antioxidant and lipid lowering potential was detected for saffron stigma, which could improve insulin resistance in obese rats. Therapeutic and protective effect of saffron is mainly related to its richness in phenolic compounds. Saffron stigma compared with petal had more notable effect, which could and should be mentioned in pharmaceutical studies.

Haloperidol increases hepatic lipid peroxidation promoted by high-fat diet in rats

This study aimed to evaluate the effects of the treatment with haloperidol (HAL) associated with a high-fat diet (HF) on hepatic and renal damage, intracellular magnesium (Mg2+) levels, and abdominal fat content. Young male Wistar rats were fed with high-fat diet or control diet during 48 weeks and, at the 24-week, part of animals began to be co-treated with HAL (1 mg/Kg/day intramuscularly). After 4 weeks of the drug administration, the livers and kidneys were removed for analyses. The results showed that HF diet significantly increased lipid peroxidation in the hepatic tissue of treated animals, when compared to animals treated with control diet (P&lt;0.05). Moreover, HF associated with HAL further increased the hepatic lipid peroxidation levels (P&lt;0.05). In contrast, HF and/or HAL did not promote significant changes in renal lipid peroxidation levels. We also found a negative correlation between intracellular Mg2+ levels and abdominal fat content among all animals. In conclusion, the data presented suggest adverse interactions between HAL and HF on liver. Furthermore, the negative correlation between the intracellular Mg2+ levels and the abdominal fat accumulation suggest a possible involvement of Mg2+ in the metabolic syndrome development associated with a HF diet.

Study on the role of flavonoids derived extract from seed residues of hippophae rhamnoides on high-fat diet induced obese mice

The objective of the paper was to explore the active mechanism underlying the role of flavonoids, which were derived from seed residues of hippophae rhamnoides (Flavonoids from the Seeds of H. rhamnoides L., FSH), in obesity. A total of 50 SPF healthy male C57BL/6 mice were selected and divided into 5 groups (with 10 mice in each group), i.e., the normal control group, the high fat diet control group, the 100 mg/kg FSH group, the 300 mg/kg FSH group, and the rosiglitazone group. The basic biochemical indicators of the mice were detected, and the liver and white adipose tissue samples were collected, stained and analyzed via Western Blot to study the effects of flavonoids on obesity. In the experiment, rosiglitazone was used as a traditional weight-inhibiting drug and its efficacy was compared with that in the FSH groups. It was found that compared with that in the high-fat diet control group, the weight gain of obese mice administered with FSH was slowed, along with reduced levels of serum total cholesterol, plasma glucose, and liver fat accumulation. Meanwhile, it was also discovered that FSH could reduce the expression of PPARγ in liver and white adipose tissues, thus helping to reduce fat accumulation. It was proved that the flavonoids derived from seed residues of hippophae rhamnoides exerted an inhibitory effect on obesity to protect the liver.

Effect of resveratrol on diabetic neuropathy in wistar albino rats

Background: Type 2 diabetes mellitus (DM) is a common chronic disease with increasing prevalence worldwide. Prolonged uncontrolled hyperglycemia, dyslipidemia are major risk factor for its complication like neuropathy. Since there is no definite treatment for diabetic neuropathy, this study aims to evaluate the effect of resveratrol on diabetic neuropathy in high fat diet with low dose streptozotocin induced type-2 DM model in wistar albino rats.Methods: First type 2 diabetic rat model was established. Wistar albino rats, fed with high-fat diet (HFD) rendered diabetic with streptozotocin, were divided into 6 groups, disease control (DC) treated with vehicle, standard control (SC) which received metformin, test groups treated with 5, 10, and 20 mg/kg b.w. of resveratrol and combination of half dose of metformin and resveratrol (10 mg/kg) (TC). A group of six normal animals served as normal control (NC), another six as HFD control. Fasting plasma glucose, lipid profile were measured one week after induction of diabetes. The animals were then treated orally for 2 weeks after which the same parameters were repeated. Behavioral biomarkers for neuropathy are measured in 4 weeks and 6 weeks of treatment. The in-vivo results were analyzed by one way ANOVA followed by Tukey’s multiple comparison test for biochemical parameters and Kruskal Wallis test followed by Dun’s multiple comparison test for behavioral biomarkers.Results: Increase in fasting plasma glucose (FPG), deranged lipid profile, increased neuropathy in DC compared to NC, HFD control while a significant decrease in FBG, improved pain behavior with SC, test groups (p&lt;0.05) as compared to the DC group.Conclusions: Resveratrol prevents diabetic neuropathy.

Ferulic acid maintains the self-renewal capacity of embryo stem cells and adipose-derived mesenchymal stem cells in high fat diet-induced obese mice

Self-renewal is required for embryo stem cells (ESCs) and adipose-derived mesenchymal stem cells (ADMSCs). This study examined the ability of ferulic acid in mouse ESCs and ADMSCs, in a high fat diet-induced mouse model. Initially, five natural compounds of ferulic acid, xanthohumol, curcumin, ascorbic acid, and quercetin were screened in ESCs using an alkaline phosphate +(AP+) assay, as a self-renewal biomarker. A ferulic acid treatment was the highest AP+ staining in hop-hit screening compounds. Also a ferulic acid increased Nanog mRNA levels in ESCs. The in vivo effects of ferulic acid were next examined in an obese mouse model. C57BL/6 J male mice were fed either a high fat diet (HFD) or control diet with ferulic acid (5 g/kg diet) for 8 weeks. Ferulic acid exhibited weight loss and improved glucose homeostasis, lipid profiling, and hepatic steatosis in a HFD-induced mouse model. Next, ADMSCs (Sca-1+CD45−), a hallmark of fat stem cells, were then isolated and quantified from mouse abdominal adipose tissue. A HFD decreased the Sca-1+CD45− cell population of ADMSCs, but HFD-induced obese mice given ferulic acid showed an increased the Sca-1+CD45− cell population of ADMSCs. Moreover, ferulic acid enhanced NANOG mRNA levels in human ADMSCs and its related gene mRNA expression. Overall, this study suggests that ferulic acid preserves self-renewal in ESCs, and contributes to ADMSCs self-renewal and effective weight control in obesity.

Prenatal ethanol exposure increased the susceptibility of adult offspring rats to glomerulosclerosis

This study was aimed to investigate the effect of prenatal ethanol exposure (PEE) on the susceptibility of offspring rats to glomerulosclerosis and to explore the mechanism. Pregnant Wistar rats were intragastrically administered ethanol (4g/kg·d) from gestational day (GD) 9 to GD 20, and the control group was given equal volume of normal saline. The offspring rats were all fed with high-fat diet after weaning, and were sacrificed at postnatal week 24 (PW24). The results revealed that the adult offspring kidneys in the male and female PEE groups exhibited higher glomerulosclerosis index and interstitial fibrosis index compared with the high-fat diet control groups, accompanied by elevated serum creatinine level. The protein expression of Nephrin and WT1, which were the marker genes of podocytes, was significantly decreased, whereas the protein expression of desmin and α-SMA, the marker genes of mesenchymal cells, was remarked enhanced in the male and female PEE groups. Compared with the high-fat diet control groups, the mRNA and protein expressions of renal angiotensin II receptor type 2 (AT2R) were decreased in the male PEE group, but increased in the female PEE group. PEE increased the mRNA and protein expressions of glucocorticoid (GC) activation system and inhibited the expression of insulin-like growth factor 1 (IGF1) signaling pathway in male offspring kidney; on the contrary, in female offspring kidney, PEE inhibited the mRNA and protein expression of glucocorticoid activation system and increased the expression of IGF1 signaling pathway. Taken together, PEE increased the susceptibility of the adult offspring to glomerulosclerosis, and the programming of renal AT2R or GC-IGF1 is respectively involved in the toxicity of PEE to the male or female offspring.

Red pepper seed water extract suppresses high-fat diet-induced obesity in C57BL/6 mice.

In this study, the protective effect of red pepper seed water extract (RPS) against the obesity in high fat diet (HFD)-fed mice was investigated (HFD control group, and HFD group treated with 100 or 200mg/kg body weight of RPS for 13weeks). The application of RPS partially reversed the HFD-induced increases in body weight and adipose tissue weight. The patterns of the adipose tissue weights were parallel to the patterns of fat area, as measured in DXA procedure. In the adipose tissue, RPS suppressed the expression of adipogenic transcription factors and adipose marker genes. AMP-activated protein kinase activation was observed in the adipose tissue by RPS treatment. In addition, RPS improved high homeostasis model assessment of insulin resistance and hyperlipidemia in HFD fed mice. These findings suggest that RPS can be used as a potential therapeutic substance for reducing body fat and obesity related diseases.

Polydatin Inhibits Adipose Tissue Inflammation and Ameliorates Lipid Metabolism in High-Fat-Fed Mice.

Polydatin (PD), an active component of Chinese herbs, is reported to have many biological functions, such as cardioprotective actions, anti-inflammatory activities, and antitumor effects. In this study, we investigated the effects of PD on body weight control, glucose and lipid metabolic regulation, and anti-inflammation in a high-fat-diet- (HFD-) induced obese mice model. After treatment of PD (100 mg/kg/d for 4 weeks), HFD mice reduced body weight, retroperitoneal fat mass, and adipose cell sizes; significantly lowered serum total cholesterol triglyceride (TG) and low-density lipoprotein (LDL) levels; and increased high-density lipoprotein (HDL) levels compared with the HFD control mice. Further studies showed that PD downregulated the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involving in the regulation of adipocyte differentiation, in the retroperitoneal fat of HFD mice. Additionally, PD significantly upregulated the mRNA and protein expressions of leptin, an adipocyte-derived anorexic hormone that regulates food intake and energy expenditure, in the adipose tissues of HFD mice. Moreover, PD reduced the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in the retroperitoneal and epididymal tissues of HFD mice, suggesting that PD prevented adipose tissue inflammation. In conclusion, PD may serve as a pharmaceutic candidate for obesity-related lipid metabolism, anti-inflammation, and body weight loss.

High-intensity interval training has a greater effect on reverse cholesterol transport elements compared with moderate-intensity continuous training in obese male rats.

The present study compares the effect of high-intensity interval training (HIIT; 18 min) and moderate-intensity continuous training (MIT; 1 h) on reverse cholesterol transport (RCT) elements in obese subjects. Thirty adult male rats were induced high-fat diet (HFD) for 12 weeks. After four weeks, the rats were randomly divided into three groups while simultaneously continuing the HFD for the remaining eight weeks. Group specificities were HFD-control, HFD-MIT and HFD-HIIT. The rats were sacrificed 48 h after the last training session and the samples were collected. Analysis of variance and Pearson's correlation test were used for the statistical analyses (significance level: p ≤ 0.05). The results showed that both HIIT and MIT improved heart ABCA1, ABCG1, ABCG4, ABCG5, ABCG8, LXR-α and PPARγ gene expression as well as plasma Apo A1, LCAT, lipids and lipoproteins (p ≤ 0.05). Moreover, higher cardiac ABCA1, ABCG1, ABCG4, ABCG5, ABCG8 and PPARγ expression and plasma high-density lipoprotein cholesterol (p ≤ 0.05) concentrations were found in the HFD-HIIT group compared with the HFD-MIT group. HIIT may have more cardioprotective effects than MIT against atherosclerosis, along with saving time, as supported by the changes observed in the main factors involved in the RCT process.

Pectin lyase-modified red ginseng extract improves glucose homeostasis in high fat diet-fed mice

Red ginseng has long been used as a traditional folk medicine for various diseases including diabetes. Recently, a preparation of red ginseng extract by pectin lyase modification has been developed and named as GS-E3D. The aim of this study is to evaluate the preventive effect of GS-E3D on hyperglycemia induced by feeding a high fat diet (HFD) in mice. GS-E3D was orally administered to C57BL/6J mice at different doses (250, 500, or 1000 mg/kg/day) for 6 weeks while on a HFD. Body weight and blood glucose were monitored weekly, and oral glucose tolerance test (OGTT) was performed at 5th week of the experiment. Glycemic indications and metabolic parameters were further measured in serum. Six weeks of GS-E3D treatment to mice significantly inhibited HFD-induced body weight gain, hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Notably, GS-E3D treated mice at doses of 250, 500 and 1000 mg/kg showed 41.8%, 45.0% and 55.1% reduction in insulin resistance index, respectively, compared to HFD control mice. OGTT revealed that GS-E3D markedly prevented steep rise of blood glucose and insulin levels after glucose challenge and ameliorated HFD-induced glucose and insulin intolerance. The histological analysis showed enlarged adipocytes in HFD-fed mice whereas the adipocyte hypertrophy was prevented in GS-E3D treated mice in a dose-dependent manner. Furthermore, when peripheral glucose uptake level was assessed by total and membranous glucose transporter type 4 (GLUT4) protein contents, GS-E3D restored GLUT4 protein expression to the levels of regular diet fed mice, and dose-dependently translocated them to the plasma membrane. The results collectively show that GS-E3D ameliorates obesity-related impaired glucose tolerance by improving insulin sensitivity in the epidydimal adipose tissue.

Toward isolating reward changes in diet-induced obesity: A demand analysis

Although hormonal and metabolic factors are well known to influence obesity, recent evidence suggests that obesity may be influenced also by changes in reward sensitivity akin to that seen in other ‘reward pathologies’, like substance use disorders. The current study sought to isolate changes in reward that may occur after the onset of diet-induced obesity by characterizing the economic demand for caloric (sucrose) and non-caloric (saccharin) reinforcers in a preclinical model of diet-induced obesity (DIO). We utilized economic demand analysis to measure baseline demand intensity (Q0) and demand elasticity (α) for sucrose and saccharin reinforcers in rats. After baseline measures were collected, rats were assigned randomly to a high-fat (HF) diet or low-fat (LF) control diet. After 8-weeks of diet exposure, HF rats were divided into obesity-resistant (OR) or obesity-prone (OP) groups based on weight after the 8-week HF diet exposure. Post-DIO demand data for each reinforcer were reassessed. At baseline, rats had higher demand intensity and lower elasticity for sucrose compared to saccharin. After 8-weeks of the high-fat diet, OP rats had significantly greater weight gain and lower demand elasticity for sucrose and saccharin and higher demand intensity for saccharin. The changes in sucrose and saccharin elasticity suggest that DIO-induced changes in food-related behavior are associated with changes in reward processes. The changes in demand intensity for saccharin suggest that demand intensity, as a measure of ‘set point’, is not directly linked to metabolic processes. The current study shows that microeconomic theory and demand analysis is able to isolate independent aspects of diet-induced reward changes related to caloric and non-caloric reinforcers.

CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis

Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental autoimmune encephalomyelitis (EAE) induction. Since CPT1a is a key molecule in lipid metabolism, we compared the effects of a high-fat diet (HFD) and normal diet (ND) on disease progression. The disease severity increased significantly in WT mice compared to that in Cpt1 P479L mice. In addition, WT mice receiving HFD showed markedly exacerbated disease course when compared either with Cpt1a P479L mice receiving HFD or WT control group receiving ND. Induction of EAE caused a significant decrease of myelin basic protein expression in the hindbrain of disease affected WT mice in comparison to Cpt1a P479L mice. Further, WT mice showed increased expression of oxidative stress markers like Nox2 and Ho-1, whereas expression of mitochondrial antioxidants regulator Pgc1α was increased in Cpt1a P479L mice. Our results suggest that, lipids metabolism play an important role in EAE, as shown by the higher severity of disease progression in both WT EAE and WT EAF HFD-fed mice in contrast to their counterpart Cpt1a P479L mutant mice. Interestingly, mice with downregulated lipid metabolism due to the Cpt1a P479L mutation showed resistance to EAE induction. These findings support a key role for CPT1A in the development of EAE and could be a promising target in MS treatment.

Maternal high fat diet programs hypothalamic-pituitary-adrenal function in adult rat offspring

Abstract Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 μg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.

Anti-Obesity Effects of the Flower of Prunus persica in High-Fat Diet-Induced Obese Mice.

Prunus persica (L.) Batsch is a deciduous fruit tree cultivated worldwide. The flower of P. persica (PPF), commonly called the peach blossom, is currently consumed as a tea for weight loss in East Asia; however, its anti-obesity effects have yet to be demonstrated in vitro or in vivo. Since PPF is rich in phytochemicals with anti-obesity properties, we aimed to investigate the effects of PPF on obesity and its underlying mechanism using a diet-induced obesity model. Male C57BL/6 mice were fed either normal diet, high-fat diet (HFD), or HFD containing 0.2% or 0.6% PPF water extract for 8 weeks. PPF significantly reduced body weight, abdominal fat mass, serum glucose, alanine transaminase and aspartate aminotransferase levels, and liver and spleen weights compared to the HFD control group. Real-time quantitative polymerase chain reaction analysis revealed that PPF suppressed lipogenic gene expression, including stearoyl-CoA desaturase-1 and -2 and fatty acid synthase, and up-regulated the fatty acid β-oxidation gene, carnitine palmitoyltransferase-1, in the liver. Our results suggest that PPF exerts anti-obesity effects in obese mice and these beneficial effects might be mediated through improved hepatic lipid metabolism by reducing lipogenesis and increasing fatty acid oxidation.

Linggui Zhugan Formula Improves Glucose and Lipid Levels and Alters Gut Microbiota in High-Fat Diet-Induced Diabetic Mice.

Background: The gut microbiota plays important roles in the occurrence and development of obesity and diabetes through participating in nutrient absorption and metabolism. Microecological regulation is likely to be key to understanding the effects of Chinese medicine. The Linggui Zhugan (LGZG) formula is a well-known Chinese medicine for controlling obesity in the clinic. However, its pharmacological effects and mechanism of action in diabetes require further exploration.Objective: To evaluate the effects of LGZG on body weight, glycemic control, lipid levels, and gut microbiota in high-fat diet-induced diabetic mice.Methods: High-fat diet-induced diabetic mice were subjected to an 8-week protocol of LGZG administration. We then evaluated the pharmacological effects of LGZG and its influence on gut microbes in fecal samples using the 16S rRNA-based microbiome profiling technique.Results: LGZG administration significantly reduced body weight and body fat mass in diabetic mice. Compared with the high-fat diet control group, LGZG favorably influenced blood glucose control, decreased blood glucose levels, and increased glucose tolerance, accompanied by an improvement in lipid metabolism. Furthermore, the global community composition and relative abundance of many taxa differed between mice fed chow or a high-fat diet. As expected, LGZG supplementation altered the general community structure of gut microbiota, the Firmicutes/Bacteroidetes ratio, and the relative abundance of certain bacteria, such as Bacteroides, Lactobacillus, Oscillospira, and Helicobacter.Conclusion: LGZG effectively controlled obesity and relieved insulin resistance, which may be closely related to its impact on gut microbiota.

NLRP3 Inflammasome Promotes Myocardial Remodeling During Diet-Induced Obesity.

Background: Obesity is an increasingly prevalent metabolic disorder in the modern world and is associated with structural and functional changes in the heart. The NLRP3 inflammasome is an innate immune sensor that can be activated in response to endogenous danger signals and triggers activation of interleukin (IL)-1β and IL-18. Increasing evidence points to the involvement of the NLRP3 inflammasome in obesity-induced inflammation and insulin resistance, and we hypothesized that it also could play a role in the development of obesity induced cardiac alterations.Methods and Results: WT, Nlrp3−/−, and ASC−/− (Pycard−/−) male mice were exposed to high fat diet (HFD; 60 cal% fat) or control diet for 52 weeks. Cardiac structure and function were evaluated by echocardiography and magnetic resonance imaging, respectively. Whereas, NLRP3 and ASC deficiency did not affect the cardiac hypertrophic response to obesity, it was preventive against left ventricle concentric remodeling and impairment of diastolic function. Furthermore, whereas NLRP3 and ASC deficiency attenuated systemic inflammation in HFD fed mice; long-term HFD did not induce significant cardiac fibrosis or inflammation, suggesting that the beneficial effects of NLRP3 inflammasome deficiency on myocardial remodeling at least partly reflect systemic mechanisms. Nlrp3 and ASC (Pycard) deficient mice were also protected against obesity-induced systemic metabolic dysregulation, as well as lipid accumulation and impaired insulin signaling in hepatic and cardiac tissues.Conclusions: Our data indicate that the NLRP3 inflammasome modulates cardiac concentric remodeling in obesity through effects on systemic inflammation and metabolic disturbances, with effect on insulin signaling as a potential mediator within the myocardium.

Effects of Piceatannol and Resveratrol on Sirtuins and Hepatic Inflammation in High-Fat Diet-Fed Mice.

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV) and considered as a potential metabolic regulator. The purpose of this study was to compare the effects of PIC and RSV on parameters affecting inflammation, oxidative stress, and sirtuins (Sirt). Male C57BL/6J mice, 20 weeks old, were assigned to the following groups; (1) lean control, (2) high-fat diet control (HF), (3) HF_PIC, and (4) HF_RSV. Oral administration of PIC and RSV (10 mg/kg/day) for 4 weeks improved glucose control as shown by decreasing levels of area under the curve (AUC) during the oral glucose tolerance test compared with HF group. PIC improved glycemic control by increasing hepatic levels of insulin receptor and AMP-activated protein kinase. PIC increased the levels of Sirt1, Sirt3, and Sirt6 and also increased two downstream targets of Sirt, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and forkhead box O1, in the liver. The inflammatory markers, interleukin (IL)-1 and IL-6, in the liver were downregulated by RSV treatment. Exposure to PIC and RSV significantly lowered hepatic levels of tumor necrosis factor-alpha. However, PIC and RSV treatments showed minimal effects on hepatic markers of oxidative stress. The levels of antioxidant enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), were only increased in livers of RSV-treated mice compared with HF control mice. In conclusion, PIC was superior to an equal concentration of RSV in the regulation of Sirt and its downstream targets as well as insulin signaling-related parameters, while RSV potentially suppressed levels of proinflammatory markers and increased NQO1 protein levels.

Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice.

Interruption of bile acid recirculation through inhibition of the apical sodium-dependent bile acid transporter (ASBT) is a promising strategy to alleviate hepatic cholesterol accumulation in non-alcoholic steatohepatitis (NASH), and improve the metabolic aspects of the disease. Potential disease-attenuating effects of the ASBT inhibitor volixibat (5, 15, and 30 mg/kg) were investigated in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice over 24 weeks. Plasma and fecal bile acid levels, plasma insulin, lipids, and liver enzymes were monitored. Final analyses included liver histology, intrahepatic lipids, mesenteric white adipose tissue mass, and liver gene profiling. Consistent with its mechanism of action, volixibat significantly increased the total amount of bile acid in feces. At the highest dose, volixibat significantly attenuated the HFD-induced increase in hepatocyte hypertrophy, hepatic triglyceride and cholesteryl ester levels, and mesenteric white adipose tissue deposition. Non-alcoholic fatty liver disease activity score (NAS) was significantly lower in volixibat-treated mice than in the HFD controls. Gene profiling showed that volixibat reversed the inhibitory effect of the HFD on metabolic master regulators, including peroxisome proliferator-activated receptor-γ coactivator-1β, insulin receptor, and sterol regulatory element-binding transcription factor 2. Volixibat may have beneficial effects on physiological and metabolic aspects of NASH pathophysiology.