Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Mechanism of Astragalus membranaceus Alleviating Acquired Hyperlipidemia Induced by High-Fat Diet through Regulating Lipid Metabolism.

Astragalus membranaceus (AM) is a food and medicinal homologous plant. The current research is aimed to investigate the beneficial effects and mechanisms of AM in treating acquired hyperlipidemia. The network pharmacology and bioinformatics analysis results showed 481 AM-related targets and 474 acquired hyperlipidemia-associated targets, and 101 candidate targets were obtained through the intersection, mainly enriched in endocrine resistance, AGE-RAGE in diabetic complications and p53 signaling pathways. Quercetin, kaempferol, calycosin, formononetin and isorhamnetin were determined as the candidate active components of AM in the treatment of acquired hyperlipidemia. Moreover, key targets of AM, namely, AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), cyclin D1 (CCND1) and estrogen receptor 1 (ESR1), were screened out, which were closely related to adipogenesis, fatty acid metabolism and bile acid metabolism. The subsequent animal experiments showed that AM extract treatment improved the lipid profiles of the high-fat diet (HFD)-fed mice by reducing lipogenesis and increasing lipolysis and lipid ß-oxidation, which were associated with the downregulating of AKT1 and CCND1, and the upregulating of VEGFA and ESR1 in liver and adipose tissue. Overall, AM alleviated acquired hyperlipidemia through regulating lipid metabolism, and AKT1, VEGFA, CCND1 and ESR1 might be the key targets.

Protective effect of orange essential oil on the formation of non-alcoholic fatty liver disease caused by high-fat diet.

The purpose of this study was to investigate the protective effect of sniffing orange essential oil (OEO) on the formation of non-alcoholic fatty liver disease (NAFLD) caused by a high-fat diet. The results confirmed that sniffing OEO could reduce obesity caused by a high-fat diet (HFD) by reducing the levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In addition, the observation of liver tissue sections showed that sniffing OEO could reduce lipid accumulation in liver cells. Further analysis by western blot analysis showed that OEO treatment made the expression levels of acetyl-CoA carboxylase (ACC) and Cytochrome P450 2E1 (CYP2E1) down-regulated and the expression levels of peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) up-regulated. These results indicate that the treatment of sniffing OEO could enhance the antioxidant capacity of mice and reduce liver damage caused by a high-fat diet. Furthermore, sniffing OEO could inhibit lipid synthesis and oxidative stress stimulated by a high-fat diet. Overall, OEO treatment had a certain protective effect on NAFLD-related diseases caused by a high-fat diet. Therefore, aromatherapy may be introduced as a treatment of long-term chronic diseases.

Effect of Standardized Hydrangea serrata (Thunb.) Ser. Leaves Extract on Body Weight and Body Fat Reduction in Overweight or Obese Humans: A Randomized Double-Blind Placebo-Controlled Study.

Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m2, were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.

Protective role of melatonin against adipose-hepatic metabolic comorbidities in experimentally induced obese rat model.

BACKGROUND: Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. MATERIALS AND METHODS: Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. RESULTS: HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. CONCLUSION: Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.

Zeaxanthin ameliorates obesity by activating the ß3-adrenergic receptor to stimulate inguinal fat thermogenesis and modulating the gut microbiota.

The stimulation of fat thermogenesis and modulation of the gut microbiota are promising therapeutic strategies against obesity. Zeaxanthin (ZEA), a carotenoid plant pigment, has been shown to prevent various diseases; however, the therapeutic mechanism for obesity remains unclear. Herein, whether ZEA improves obesity by activating the ß3-adrenergic receptor (ß3-AR) to stimulate white adipose tissue (WAT) thermogenesis and modulating the gut microbiota was investigated. C57BL6/N mice were fed a high-fat diet (HFD) supplemented with ZEA for 22 weeks. ZEA treatment reduced body weight, fat weight, adipocyte hypertrophy, liver weight, and lipid deposition, and improved dyslipidaemia, serum GPT, GOT, leptin, and irisin levels, glucose intolerance, and insulin resistance in HFD-fed mice. Mechanistically, ZEA treatment induced the expression of ß3-AR and thermogenic factors, such as PRDM16, PGC-1α, and UCP1, in inguinal WAT (iWAT) and brown adipose tissue. ZEA treatment stimulated iWAT thermogenesis through the synergistic cooperation of key organelles, which manifested as an increased expression of lipid droplet degradation factors (ATGL, CGI-58 and pHSL), mitochondrial biogenesis factors (Sirt1, Nrf2, Tfam, Nampt and Cyt-C), peroxisomal biogenesis factors (Pex16, Pex19 and Pmp70), and ß-oxidation factors (Cpt1, Cpt2, Acadm and Acox1). The thermogenic effect of ZEA was abolished by ß3-AR antagonist (SR59230A) treatment. Additionally, dietary supplementation with ZEA reversed gut microbiota dysbiosis by regulating the abundance of Firmicutes, Clostridia, Proteobacteria, and Desulfovibrio, which were associated with the thermogenesis- and obesity-associated indices by Spearman's correlation analysis. Functional analysis of the gut microbiota indicated that ZEA treatment significantly enriched the lipid metabolism pathways. These results demonstrate that ZEA is a promising multi-target functional food for the treatment of obesity by activating ß3-AR to stimulate iWAT thermogenesis, and modulating the gut microbiota.

Effect of Decaffeinated Green Tea Polyphenols on Body Fat and Precocious Puberty in Obese Girls: A Randomized Controlled Trial.

Background: Obesity has been reported to be an important contributing factor for precocious puberty, especially in girls. The effect of green tea polyphenols on weight reduction in adult population has been shown, but few related studies have been conducted in children. This study was performed to examine the effectiveness and safety of decaffeinated green tea polyphenols (DGTP) on ameliorating obesity and early sexual development in girls with obesity. Design: This is a double-blinded randomized controlled trial. Girls with obesity aged 6-10 years old were randomly assigned to receive 400 mg/day DGTP or isodose placebo orally for 12 weeks. During this period, all participants received the same instruction on diet and exercise from trained dietitians. Anthropometric measurements, secondary sexual characteristics, B-scan ultrasonography of uterus, ovaries and breast tissues, and related biochemical parameters were examined and assessed pre- and post-treatment. Results: Between August 2018 and January 2020, 62 girls with obesity (DGTP group n = 31, control group n = 31) completed the intervention and were included in analysis. After the intervention, body mass index, waist circumference, and waist-to-hip ratio significantly decreased in both groups, but the percentage of body fat (PBF), serum uric acid (UA), and the volumes of ovaries decreased significantly only within the DGTP group. After controlling confounders, DGTP showed a significantly decreased effect on the change of PBF (ß = 2.932, 95% CI: 0.214 to 5.650), serum UA (ß = 52.601, 95% CI: 2.520 to 102.681), and ovarian volumes (right: ß = 1.881, 95% CI: 0.062 to 3.699, left: ß = 0.971, 95% CI: 0.019 to 1.923) in girls with obesity. No side effect was reported in both groups during the whole period. Conclusion: DGTP have shown beneficial effects of ameliorated obesity and postponed early sexual development in girls with obesity without any adverse effects. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT03628937], identifier [NCT03628937].

Kombuchas from green and black teas reduce oxidative stress, liver steatosis and inflammation, and improve glucose metabolism in Wistar rats fed a high-fat high-fructose diet.

The aim of this study was to evaluate the effect of green and black tea kombuchas consumption on adiposity, lipid and glucose metabolism, liver steatosis, oxidative stress, and inflammation in Wistar rats fed a high-fat high-fructose (HFHF) diet. Wistar rats, after 8 weeks to induce metabolic alterations, were divided into an AIN-93M control group, HFHF control group, green tea kombucha + HFHF diet (GTK group), and black tea kombucha + HFHF diet (BTK group), for 10 weeks. The kombuchas improved glucose metabolism, plasma total antioxidant capacity, superoxide dismutase activity, and decreased nitric oxide concentration. Moreover, both kombuchas reduced systemic inflammation by decreasing the neutrophil/lymphocyte ratio (NLR), reduced the total adipose tissue and blood triglyceride, and reverted liver steatosis (from grade 2 to 1), besides the modulation of genes related to adipogenesis and ß-oxidation. Therefore, kombuchas from green and black teas have bioactive properties that can help control metabolic alterations induced by the HFHF diet.

Protective and proliferative effect of Aesculus indica extract on stressed human adipose stem cells via downregulation of NF-κB pathway.

Inflammatory microenvironment after transplantation affects the proliferation and causes senescence of adipose-derived mesenchymal stem cells (hADMSCs) thus compromising their clinical efficacy. Priming stem cells with herbal extracts is considered very promising to improve their viability in the inflammatory milieu. Aesculus indica (A. indica) is used to treat many inflammatory diseases in Asia for decades. Herein, we explored the protective role of A. indica extract on human adipose-derived Mesenchymal Stem Cells (hADMSCs) against Monosodium Iodoacetate (MIA) induced stress in vitro. A. indica ameliorated the injury as depicted by significantly enhanced proliferation, viability, improved cell migration and superoxide dismutase activity. Furthermore, reduced lactate dehydrogenase activity, reactive oxygen species release, senescent and apoptotic cells were detected in A. indica primed hADMSCs. Downregulation of NF-κB pathway and associated inflammatory genes, NF-κB p65/RelA and p50/NF-κB 1, Interleukin 6 (IL-6), Interleukin 1 (IL-1ß), Tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 13 (MMP-13) were observed in A. indica primed hADMSCs as compared to stressed hADMSCs. Complementary to gene expression, A. indica priming reduced the release of transcription factor p65, inhibitory-κB kinase (IKK) α and ß, IL-1ß and TNF-α proteins expression. Our data elucidates that A. indica extract preconditioning rescued hADMSCs against oxidative stress and improved their therapeutic potential by relieving inflammation through regulation of NF-κB pathway.

Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals.

We hypothesized whether propofol or active propofol component (2,6-diisopropylphenol [DIPPH] and lipid excipient [LIP-EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity-inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6-DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL-6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL-6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95-5.20]; p = .04) and its active component (2,6-DIPPH) (4.09[1.67-5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6-DIPPH increased IL-10 expression (7.59[6.28-12.95]; p = .001) in adipose tissue-derived macrophages. Additionally, 2,6-DIPPH increased C-X-C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23-29.01]; p = .02; 1.55[1.49-3.43]; p = .02) and adipose tissues (8.78[4.15-11.57]; p = .03; 2.86[2.17-3.71]; p = .01), as well as improved lung-derived neutrophil migration (28.00[-3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.

Hybrid chitosan-lipid nanoparticles of green tea extract as natural anti-cellulite agent with superior in vivo potency: full synthesis and analysis.

The aim of this work is to exploit the advantages of chitosan (CS) as a nanocarrier for delivery of anti-cellulite drug, green tea extract (GTE), into subcutaneous adipose tissue. Primarily, analysis of herbal extract was conducted via newly developed and validated UPLC method. Ionic gelation method was adopted in the preparation of nanoparticles where the effect lecithin was investigated resulting in the formation of hybrid lipid-chitosan nanoparticles. Optimal formula showed a particle size of 292.6 ± 8.98 nm, polydispersity index of 0.253 ± 0.02, zeta potential of 41.03 ± 0.503 mV and an entrapment efficiency percent of 68.4 ± 1.88%. Successful interaction between CS, sodium tripolyphosphate (TPP) and lecithin was confirmed by Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction. Morphological examination was done using transmission electron microscope and scanning electron microscope confirmed spherical uniform nature of GTE load CS-TPP nanoparticles. Ex vivo permeation study revealed permeability enhancing activity of the selected optimal formula due to higher GTE deposition in skin in comparison to GTE solution. Moreover in vivo study done on female albino Wistar rats carried out for 21 days proved successful potential anti-cellulite activity upon its application on rats' skin. Histological examination showed significant reduction of adipocyte perimeter and area and fat layer thickness. Results of the current study demonstrated that the developed GTE-loaded CS-TPP nanoparticle comprised of chitosan and lecithin showed permeability enhancing activity along with the proven lipolytic effect of green tea represent a promising delivery system for anti-cellulite activity.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system.

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

Mechanisms and Effect of Coptidis Rhizoma on Obesity-Induced Inflammation: In Silico and In Vivo Approaches.

Obesity is characterized as a chronic, low-grade inflammation state accompanied by the infiltration of immune cells into adipose tissue and higher levels of inflammatory cytokines and chemokines. This study aimed to investigate the mechanisms and effects of Coptidis Rhizoma (CR) on obesity and its associated inflammation. First, we applied a network pharmacology strategy to search the target genes and pathways regulated by CR in obesity. Next, we performed in vivo experiments to confirm the antiobesity and anti-inflammatory effects of CR. Mice were assigned to five groups: normal chow (NC), control (high-fat diet (HFD)), HFD + CR 200 mg/kg, HFD + CR 400 mg/kg, and HFD + metformin 200 mg/kg. After 16 weeks of the experimental period, CR administration significantly reduced the weight of the body, epididymal fat, and liver; it also decreased insulin resistance, as well as the area under the curve of glucose in the oral glucose tolerance test and triglyceride in the oral fat tolerance test. We observed a decrease in adipose tissue macrophages (ATMs) and inflammatory M1 ATMs, as well as an increase in anti-inflammatory M2 ATMs. Gene expression levels of inflammatory cytokines and chemokines, including tumor necrosis factor-α, F4/80, and C-C motif chemokine (CCL)-2, CCL4, and CCL5, were suppressed in adipose tissue in the CR groups than levels in the control group. Additionally, histological analyses suggested decreased fat accumulation in the epididymal fat pad and liver in the CR groups than that in the control group. Taken together, these results suggest that CR has a therapeutic effect on obesity-induced inflammation, and it functions through the inhibition of macrophage-mediated inflammation in adipose tissue.

Krill Oil Treatment Increases Distinct PUFAs and Oxylipins in Adipose Tissue and Liver and Attenuates Obesity-Associated Inflammation via Direct and Indirect Mechanisms.

The development of obesity is characterized by the metabolic overload of tissues and subsequent organ inflammation. The health effects of krill oil (KrO) on obesity-associated inflammation remain largely elusive, because long-term treatments with KrO have not been performed to date. Therefore, we examined the putative health effects of 28 weeks of 3% (w/w) KrO supplementation to an obesogenic diet (HFD) with fat derived mostly from lard. The HFD with KrO was compared to an HFD control group to evaluate the effects on fatty acid composition and associated inflammation in epididymal white adipose tissue (eWAT) and the liver during obesity development. KrO treatment increased the concentrations of EPA and DHA and associated oxylipins, including 18-HEPE, RvE2 and 14-HDHA in eWAT and the liver. Simultaneously, KrO decreased arachidonic acid concentrations and arachidonic-acid-derived oxylipins (e.g., HETEs, PGD2, PGE2, PGF2α, TXB2). In eWAT, KrO activated regulators of adipogenesis (e.g., PPARγ, CEBPα, KLF15, STAT5A), induced a shift towards smaller adipocytes and increased the total adipocyte numbers indicative for hyperplasia. KrO reduced crown-like structures in eWAT, and suppressed HFD-stimulated inflammatory pathways including TNFα and CCL2/MCP-1 signaling. The observed eWAT changes were accompanied by reduced plasma leptin and increased plasma adiponectin levels over time, and improved insulin resistance (HOMA-IR). In the liver, KrO suppressed inflammatory signaling pathways, including those controlled by IL-1ß and M-CSF, without affecting liver histology. Furthermore, KrO deactivated hepatic REL-A/p65-NF-κB signaling, consistent with increased PPARα protein expression and a trend towards an increase in IkBα. In conclusion, long-term KrO treatment increased several anti-inflammatory PUFAs and oxylipins in WAT and the liver. These changes were accompanied by beneficial effects on general metabolism and inflammatory tone at the tissue level. The stimulation of adipogenesis by KrO allows for safe fat storage and may, together with more direct PPAR-mediated anti-inflammatory mechanisms, attenuate inflammation.

Adipose and non-adipose perspectives of plant derived natural compounds for mitigation of obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyto-preparations and phyto-compounds, by their natural origin, easy availability, cost-effectiveness, and fruitful traditional uses based on accumulated experiences, have been extensively explored to mitigate the global burden of obesity. AIM OF THIS REVIEW: The review aimed to analyse and critically summarize the prospect of future anti-obesity drug leads from the extant array of phytochemicals for mitigation of obesity, using adipose related targets (adipocyte formation, lipid metabolism, and thermogenesis) and non-adipose targets (hepatic lipid metabolism, appetite, satiety, and pancreatic lipase activity). Phytochemicals as inhibitors of adipocyte differentiation, modulators of lipid metabolism, and thermogenic activators of adipocytes are specifically discussed with their non-adipose anti-obesogenic targets. MATERIALS AND METHODS: PubMed, Google Scholar, Scopus, and SciFinder were accessed to collect data on traditional medicinal plants, compounds derived from plants, their reported anti-obesity mechanisms, and therapeutic targets. The taxonomically accepted name of each plant in this review has been vetted from "The Plant List" (www.theplantlist.org) or MPNS (http://mpns.kew.org). RESULTS: Available knowledge of a large number of phytochemicals, across a range of adipose and non-adipose targets, has been critically analysed and delineated by graphical and tabular depictions, towards mitigation of obesity. Neuro-endocrinal modulation in non-adipose targets brought into sharp dual focus, both non-adipose and adipose targets as the future of anti-obesity research. Numerous phytochemicals (Berberine, Xanthohumol, Ursolic acid, Guggulsterone, Tannic acid, etc.) have been found to be effectively reducing weight through lowered adipocyte formation, increased lipolysis, decreased lipogenesis, and enhanced thermogenesis. They have been affirmed as potential anti-obesity drugs of future because of their effectiveness yet having no threat to adipose or systemic insulin sensitivity. CONCLUSION: Due to high molecular diversity and a greater ratio of benefit to risk, plant derived compounds hold high therapeutic potential to tackle obesity and associated risks. This review has been able to generate fresh perspectives on the anti-diabetic/anti-hyperglycemic/anti-obesity effect of phytochemicals. It has also brought into the focus that many phytochemicals demonstrating in vitro anti-obesogenic effects are yet to undergo in vivo investigation which could lead to potential phyto-molecules for dedicated anti-obesity action.

The Mechanism of Oral Melatonin Ameliorates Intestinal and Adipose Lipid Dysmetabolism Through Reducing Escherichia Coli-Derived Lipopolysaccharide.

BACKGROUND & AIMS: Gut microbiota have been reported to be sensitive to circadian rhythms and host lipometabolism, respectively. Although melatonin-mediated beneficial efforts on many physiological sites have been revealed, the regulatory actions of oral melatonin on the communication between gut microbiota and host are still not clear. Angiopoietin-like 4 (ANGPTL4) has been shown to be strongly responsible for the regulation of systemic lipid metabolism. Herein, we identified that oral melatonin improved lipid dysmetabolism in ileum and epididymal white adipose tissue (eWAT) via gut microbiota and ileac ANGPTL4. METHODS: Analyses of jet-lag (JL) mice, JL mice with oral melatonin administration (JL+MT), and the control for mRNA and protein expression regarding lipid uptake and accumulation in ileum and eWAT were made. Gut microbiome sequencing and experimental validation of target strains were included. Functional analysis of key factors/pathways in the various rodent models, including the depletion of gut microbiota, mono-colonization of Escherichia coli, and other genetic intervention was made. Analyses of transcriptional regulation and effects of melatonin on E coli-derived lipopolysaccharide (LPS) in vitro were made. RESULTS: JL mice have a higher level of ileal lipid uptake, fat accumulation in eWAT, and lower level of circulating ANGPTL4 in comparison with the control mice. JL mice also showed a significantly higher abundance of E coli and LPS than the control mice. Conversely, oral melatonin supplementation remarkably reversed these phenotypes. The test of depletion of gut microbiota further demonstrated that oral melatonin-mediated improvements on lipometabolism in JL mice were dependent on the presence of gut microbiota. By mono-colonization of E coli, LPS has been determined to trigger these changes similar to JL. Furthermore, we found that LPS served as a pivotal link that contributed to activating toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3_/REV-ERBα) signaling to up-regulate nuclear factor interleukin-3-regulated protein (NFIL3) expression, resulting in increased lipid uptake in ileum. In MODE-K cells, the activation of NFIL3 has further been shown to inhibit ANGPTL4 transcription, which is closely associated with lipid uptake and transport in peripheral tissues. Finally, we confirmed that melatonin inhibited LPS via repressing the expression of LpxC in E coli. CONCLUSIONS: Overall, oral melatonin decreased the quantity of E coli-generated LPS, which alleviated NFIL3-induced transcriptional inhibition of ANGPTL4 through TLR4/IL-22/STAT3 signaling in ileum, thereby resulting in the amelioration of ileal lipid intake and lower fat accumulation in eWAT. These results address a novel regulation of oral melatonin originating from gut microbiota to host distal tissues, suggesting that microbe-generated metabolites are potential therapies for melatonin-mediated improvement of circadian rhythm disruption and related metabolic syndrome.

Carotenoids obtained from an ionic liquid-mediated process display anti-inflammatory response in the adipose tissue-liver axis.

Ionic liquids (ILs) have been proposed as more efficient and sustainable solvents to replace volatile organic solvents (VOSs). However, the drawbacks associated with their use are still limiting the regular application of bioactive compounds obtained from the processes they mediate as food ingredients. It is true that the number of ILs approved by the Food and Drug Administration for food applications is still low and mainly focused on the ones from the quaternary ammonium family. However, this trend is changing, judging from the evidence that industries are surpassing overgeneralization about ILs (on price and toxicity) and starting to consider the potential and performance of ILs as solvents. Despite the examples of industries applying ILs in their processes, the use of bioactive compounds obtained from IL-based processes as ingredients in food formulations is still a big challenge. The positive influence of carotenoids on diseases associated or originating from the inflammatory scenario including, among others, obesity, is not new. Moreover, it is also well known that the poorest population worldwide does not have the recommended intake of carotenoids, especially those pro-vitaminic A. In an attempt to help answer this issue, dietary supplements containing adequate doses of natural carotenoids are expected to be the solution, or at least, part of the solution for a healthier life, but also, to reduce hunger. Thus, complete studies evaluating the toxicological potential and the real viability of adding these bioactive compounds in food formulations proving (or not!) their safety to consumers and handlers are highly demanded. This work proposes to investigate the potential of carotenoids extracted from Bactris gasipaes feedstocks mediated by an ethanolic solution of an imidazolium-based IL. Thus, male Wistar rats were randomized in six different groups, supplemented or not by carotenoids extracted by IL or VOS, and fed by control- and/or high-fat-diets (HFD). The adipose tissue-liver axis was studied as a model to investigate the influence of the carotenoids on the levels of inflammation and oxidative stress markers. The main results showed that animals supplemented with carotenoids extracted with IL displayed improvements in serum parameters, besides lower metabolic efficiency, and antioxidant response on the liver, even when fed with HFD. However, animals supplemented with carotenoids extracted by VOS showed higher levels of pro-inflammatory markers and huge oxidative stress on the liver.

Supplementation of cumin seed powder prevents oxidative stress, hyperlipidemia and non-alcoholic fatty liver in high fat diet fed rats.

The present investigation was an attempt to evaluate the hypoglycemic, lipid-lowering, antioxidant and hepatoprotective effects of cumin (Cuminum cyminum family: Apiaceae) supplementation in high fat (HF) diet fed rats. Male Wistar rats were divided into four groups, such as control, control+ cumin, HF and HF+ cumin. Oral glucose tolerance test, plasma lipids, oxidative stress parameters, antioxidant enzymes activities, and liver dysfunction marker enzyme activities were evaluated. Additionally, histological staining of liver tissue was performed to evaluate the inflammatory cells infiltration, iron deposition and fibrosis. The current investigation demonstrated that 1% (w/w) supplementation of cumin powder significantly reduced HF diet-induced glucose intolerance, epididymal and mesenteric fat wet weights and lipid parameters like triglycerides, total cholesterol and low-density lipoproteins. Oxidative stress-related biomarkers including thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and advanced oxidation protein product (APOP) were also reduced by cumin supplementation. Moreover, HF-diet increased the activity of hepatic biomarker enzymes such as alanine transaminase (ALT) and alkaline phosphatase (ALP) activities which were significantly reduced by cumin powder supplementation. On the other hand, cumin powder supplementation was able to restore the reduced glutathione level with parallel augmentation of the antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase in liver of HF diet-fed rats. Additionally, histological assessments confirmed that cumin powder supplementation also normalized the fat droplet deposition and inflammatory cells infiltration in the liver of HF diet-fed rats. This study suggests that cumin powder supplementation ameliorates dyslipidemia, oxidative stress and hepatic damage in HF diet-fed rats.

Pharmacopuncture of Taraxacum platycarpum extract reduces localized fat by regulating the lipolytic pathway.

Localized fat deposits are associated with health and aesthetic problems that mainly affect a large proportion of individuals. Recently, bioactive constituents of TP have been reported to affect lipid metabolism. In this study, we performed a network pharmacological analysis to assume potential lipolytic effects of TP and investigated the actual lipolytic effects of TP extract injection on local body fat and its underlying mechanism. Using the genes related to active compounds of TP, the network was constructed. Through the Functional Enrichment Analysis, Lipid Metabolism and Fatty Acid Metabolism were expected to be affiliated with the network, which implied possible lipolytic effects of TP. On the comparison between TP network and Obesity-related Gene Sets, about three-fourths of elements were in common with the gene sets, which indicated a high relevance between TP and obesity. Based on the genes in lipolysis-related pathways, Perilipin, CGI-58, ATGL, HSL and MGL were selected to identify the actual lipolytic effects of TP. TP injection reduced the inguinal fat weight. Also, the diameter of the adipocytes was decreased by the TP treatment in HFD-induced obese mice. In addition, TP suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. Moreover, because the expression of Perilipin was increased, CGI-58, ATGL, HSL and MGL were markedly decreased. Furthermore, glycerol release was down-regulated by the TP treatment. TP exerted its lipolytic effects by regulating the lipolysis machinery through stimulation of lipases. Based on the present findings, TP is expected to be a potent component of injection lipolysis for removing localized body fat.

Increased pro-inflammatory cytokines in ovary and effect of γ-linolenic acid on adipose tissue inflammation in a polycystic ovary syndrome model.

Polycystic Ovary Syndrome (PCOS), a major endocrine disorder, affects the reproductive function of a woman, along with an association with metabolic conditions like insulin resistance and inflammation. The inflammatory nature of PCOS is much debated over, owing to numerous cases of elevation in cytokine levels. Studies have shown the beneficiary effect of Gamma-Linolenic acid (GLA) in reducing inflammation related to many conditions such as atopic dermatitis, rheumatoid arthritis, arterial disease, obesity, and even PCOS. The study aims at assessing the expression of inflammatory cytokines in the ovary and Peri-ovarian adipose tissue (POAT) of the Dehydroepiandrosterone (DHEA) induced PCOS rat model. Further, this study also evaluates the effect of γ-linolenic Acid (GLA) on these cytokines in POAT. Female Wistar rats were subcutaneously injected with 60 mg/kg DHEA daily for 28 days. These PCOS-induced rats were then orally administered with 50 mg/kg GLA for 14 days. The gene expression of cytokines was assessed by Real Time-PCR. The study showed an increase in the expression of cytokines in the ovary and POAT of the DHEA group. This suggests the role of ovarian adipose in adding to the pro-inflammatory state of PCOS. Moreover, the administration of GLA to the PCOS-induced rats resulted in a reduction of cytokine expression from the POAT, indicating that the compound was successful in reducing the associated inflammation. The study throws light on the possibility of using GLA as a supplementary or naturalistic alternative in ameliorating ovarian adipose-associated inflammation that accompanies PCOS.