High-fed Diet Research Articles

Environment friendly green synthesis method based natural bioactive functional “catechin and gingerol” loaded nanomedicine for the management of obesity

Obesity is one of the major health problems across the world and the leading cause of death. Natural bioactive functional compounds (catechin, Cat and gingerol, Gin) have been reported to control obesity. The application of a nanoparticulate (NPs) delivery system has shown greater efficacy in the treatment of different diseases. The present study was designed to prepare the Cat-Gin silver nanoparticles (AgNPs) using the microwave method. The prepared Cat-Gin-AgNPs were characterized for particle size, zeta potential, encapsulation efficiency and drug release. Further, it was evaluated for anti-obesity activity (body weight, total abdominal fat, lipid profile and liver profile) using a high-fed diet (HFD) induced obesity model. The formulated Cat-Gin-AGNPs showed nano-metric size (110 ± 4.65 nm), polydispersity index (PDI) of 0.27 ± 0.03, and surface charge (−17.6 ± 2.6 mV) with a spherical shape. It also depicted high encapsulation efficiency (<80 %) with prolonged drug release behaviour (Cat – 84.34 ± 4.12 % and Gin – 72.33 ± 3.87 %). The in vivo study parameters revealed a significant (p ≤ 0.001) reduction in body weight, food intake and total abdominal fat. The biochemical results displayed a reversal in altered biochemical parameters to the normal range (Group 4) as compared to HFD control (Group 2). It also helps restored the liver enzymes in obese rats. The results of the study highlighted the applicability of Cat-Gin-AGNPs as a novel delivery system in the treatment of obesity.

Effects of magnesium picolinate, zinc picolinate, and selenomethionine co-supplementation on reproductive hormones, and glucose and lipid metabolism-related protein expressions in male rats fed a high-fat diet

This study aimed to examine the impacts of the magnesium picolinate (MgPic), zinc picolinate (ZnPic), and selenomethionine (SeMet) alone or as a combination on blood metabolites, oxidative enzymes, reproductive hormones, and glucose and lipid metabolism-related protein expressions in Wistar rats fed a high-fed diet (HFD). The rats were fed either a control, HFD, or HFD supplemented with a single (MgPic, ZnPic, SeMet) or two or three organic mineral combinations. Body weights, visceral fat, serum glucose, insulin, total cholesterol, triglycerides, leptin, malondialdehyde (MDA) concentrations as well as liver sterol regulatory element-binding protein-1c (SREBP-1c), liver X receptor alpha (LXRα), ATP citrate lyase (ACLY), fatty acid synthase (FAS), and nuclear factor kappa B (NF-κB) levels increased, while serum testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF-1) concentrations along with liver nuclear factor erythroid 2-related factor 2 (Nrf2) levels declined in HFD rats (P < 0.05). Supplementing each organic mineral, but particularly the combination of HFD + MgPic + ZnPic + SeMet reversed the responses with various degrees. None of the organic elements alone or as a combination of two exerted a prominent effect on parameters measured. Although not additive or synergistic, the combination of all organic minerals added to HFD (HFD + MgPic + ZnPic + SeMet) provided the greatest responses.

Hydroxychloroquine Improves Obesity-Associated Insulin Resistance and Hepatic Steatosis by Regulating Lipid Metabolism.

The burden of obesity and associated cardiometabolic diseases has been considered as an important risk factor for lupus patients. Therefore, whether obesity is involved in the over-activation of autoimmune response has attracted more and more attention. Hydroxychloroquine is a synthetic antimalarial drug and has been the clinical treatment of rheumatic diseases irreplaceable first-line drugs. Hydroxychloroquine has been suggested to have beneficial effects on lipids and insulin sensitivity, which may contribute in lowering high cardiovascular risk in SLE patients. However, its mechanism on insulin sensitivity and lipid disorders is far from being completely understood. In the present study, the therapeutic effects of hydroxychloroquine were evaluated under pathological conditions in vivo. Obesity was induced in C57BL/6 mice fed with high-fed diet, or in mice fed with high-fat diet and hydroxychloroquine. In addition, healthy mice that received normal chow diet were also monitored. The present results revealed that hydroxychloroquine reduced weight, hepatic steatosis, glucose, and insulin resistance. Furthermore, hydroxychloroquine downregulated the expression of peroxisome proliferator-activated receptor gamma in the liver. According to these present results, genes about lipid metabolism went down in high-fat mice liver. Hydroxychloroquine shows potential in ameliorating obesity-induced pathology, which acts though PPARγ to facilitate the healthy function of hepatic tissues. This evidence shows that hydroxychloroquine plays a role in improving obesity-induced lipotoxicity and insulin resistance though the peroxisome proliferator-activated receptor gamma pathway.

Wnt/β-Catenin Signaling and Obesity.

Obesity has become epidemic worldwide, which triggers several obesity-associated complications. Obesity is characterized by excess fat storage mainly in the visceral white adipose tissue (vWAT), subcutaneous WAT (sWAT), and other tissues. Myriad studies have demonstrated the crucial role of canonical Wnt/β-catenin cascade in the development of organs and physiological homeostasis, whereas recent studies show that genetic variations/mutations in the Wnt/β-catenin pathway are associated with human metabolic diseases. In this review, we highlight the regulation of updated Wnt/β-catenin signaling in obesity, especially the distinctly depot-specific roles between subcutaneous and visceral adipose tissue under high-fed diet stimulation and WAT browning process.

ERK-dependent mTOR pathway is involved in berberine-induced autophagy in hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate-palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis. Our data demonstrated that BBR had profound effects on improving hepatic lipid accumulation both in vivo and in vitro, and led to high autophagy flux. The molecular alterations proceeding these changes were characterized by inhibition of the ERK/mTOR pathway. These findings suggest an important mechanism for the positive effects of BBR on hepatic steatosis, and may provide new evidence for the clinical use of BBR in NAFLD.

Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress

Ethnopharmacological relevanceSchisandra chinensis (Turcz.) Baill. (SC) is a traditional Chinese herbal medicine with diverse pharmacological activities for treatment of various human diseases. Endoplasmic reticulum (ER) stress is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of methanol extract of Schisandra chinensis (SC extract) against ER stress-induced NAFLD in vitro and in vivo. Material and methodsThe protective effects of SC extract were examined in tunicamycin- or palmitate-treated HepG2 cells in vitro, and in tunicamycin-injected mice or high fed diet (HFD) obese mice in vivo. Expression of ER stress markers including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), and triglyceride accumulation were measured in HepG2 cells and in the liver of mice. ResultsSC extract significantly inhibited expression of tunicamycin-induced ER stress markers in tunicamycin-treated HepG2 cells and in the liver of tunicamycin-injected mice, and it also inhibited tunicamycin-induced triglyceride accumulation. Similar observations were made under physiological ER stress conditions such as in palmitate-treated HepG2 cells and in the liver of HFD obese mice. In addition, SC extract repressed the expression of inflammatory genes and lipogenic genes in palmitate-treated HepG2 cells. Schisandrin, an abundant bioactive lignan in SC extract, inhibited the expression of ER stress markers in tunicamycin-or palmitate-treated HepG2 cells, whereas Gomisin J did not affect ER stress markers. ConclusionsSC attenuates ER stress and prevents development of NAFLD. SC may be useful as a pharmacological agent for protection against ER stress-induced human diseases.

산초 추출물의 췌장 리파아제 저해 및 지질대사에 미치는 영향

Abstract Obesity is the most common nutritional disorder in the developed world and has become a global epidemic in recent years. In this study, Zanthoxylum planispinum extracts (ZPE) were evaluated on the effect on inhibition of pancreatic lipase and lipid metabolism by oral treatment for 2 months in high-fed diet obesity-induced Balb/c mice. The ZPE showed pancreatic lipase inhibitory activity with IC 50 of 0.3 ㎍/㎖. No significant difference in feed intake was observed among the groups. The high-fat diet-treated Z. planispinum extracts groups (HFD+ZPE, 100 ㎎/㎏) significantly decreased body weight compared to the high-fat diet vehicle groups (HFD, p<0.05). The high-fat diet-treated Xenical groups (HFD+Xenical, n=10, 30 ㎎/㎏) also showed a significant reduction of body weight compared to HFD (p<0.05). Biochemical parameters (triglyceride, total cholesterol, and high-density lipoprotein cholesterol) in HFD plus ZPE diet groups were significantly lower than those of the HFD groups (p<0.05). These results indicated that ZPE more effectively suppressed the effects of HFD on body fat gain with the inhibitory effect on pancreatic lipase. Key words: obesity, Zanthoxylum planispinum, pancreatic lipase, biochemical parameter

PS1 - 6. Pyridoxamine improves adiposity and insulin resistance in high-fed diet induced obese mice

Obesity is characterized by a dysregulation of pro- and anti-inflammatory adipokines which are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. We showed that the advanced glycation endproduct (AGE), Ne-(Carboxymethyl)lysine (CML), accumulates in adipose tissue in obesity and that CML, via the receptor for AGEs (RAGE) leads to inflammatory adipokines.

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile.

Penggunaan Infusa Daun Rambutan (Nepheleum Lappacoum L.) sebagai Anti Atherosklerosis

Recently, there have been many investigations on the relationship between hypercholesterolemia and cardiovascular disease, which is becoming the main health problem now. Past studies of polyphenols have been shown to promote hypolipidemia. The objective of this study was to determine whether tannins in Rambutan leaf could act to reduce lipid plaque in organs. Male Wistar rats (160 – 180 g body wt) were included in the study. Before the experimental procedure, they were assigned to one of five groups: a normal group with a standard diet, a control group fed a high-fed diet, a simvastatin treatment group fed a high-fat diet, a rambutan leaf infusion 7.2 % treatment group fed a high-fat diet and a rambutan leaf infusion 28.8 % treatment group fed a high-fat diet. Blood pressure was measured on 0 day, 21st, and 49th day. The study showed that 28.8 % rambutan leaf infusion significantly reduced blood pressure to normal. Lipid plaque was analyzed qualitatively used haematoxylin-eosin. The result suggested that lipid plaque was reduced by 7.2 % rambutan leaf infusion. To sum up, rambutan leaf infusion could reduce blood pressure to normal in 28.8%. Otherwise, lipid plaque was reduced by 7.2% rambutan leaf infusion. keyword : hypercholesterolemia, tannin, rambutan leaf infusion