Impacts of an 8-week regimen of aged garlic extract and aerobic exercise on the levels of Fetuin-A and inflammatory markers in the liver and visceral fat tissue of obese male rats.

BACKGROUND & AIMS: Obesity-induced chronic low-grade systemic inflammation is linked to the development of numerous diseases. Fetuin-A is known to affect inflammation and insulin resistance in obesity conditions. Free fatty acid (FFA)-induced proinflammatory cytokine expression in adipocytes occurs only in the presence of both Fetuin-A and toll-like receptor 4 (TLR4) and removing either of them prevented FFA-induced insulin resistance. Aged garlic extract (AGE) and exercise training have anti-inflammatory effects; however, the impact of AGE on Fetuin-A is unknown. We examined the effects of AGE with or without aerobic training (AT) on Fetuin-A and inflammatory markers. METHODS: Forty healthy male Sprague Dawley rats were randomly assigned to normal diet (ND) (n = 8) or high-fat diet (HFD) groups (n = 32) and fed for 9 weeks. After 9 weeks ND group continued normal diet, and the HFD group was randomly assigned to the HFD, HFD + AGE (600 mg/kg, once daily), HFD + AT (5 days/week), and HFD + AGE + AT groups that were continued for 8 weeks (n = 8). The significance of differences among groups was assessed using one-way analysis of variance followed by the post-hoc Tukey test. Statistically significant differences were considered for p < 0.05. RESULTS: AGE, AT, and AGE + AT significantly decreased body weight, plasma Fetuin-A, HOMA-IR, mRNA and protein levels of Fetuin-A and NFƙB in the liver and mRNA and Protein levels of Fetuin-A, TLR4 and NFƙB in visceral adipose tissue (VAT) compared to HFD. However, only AGE + AT significantly decreased TLR4 protein levels in the liver. CONCLUSION: Although AT and AGE reduce Fetuin-A and inflammatory markers, a combination of the two may be more effective at lowering inflammation.

Unraveling the Connection: Visceral Adipose Tissue and Vitamin D Levels in Obesity.

Vitamin D deficiency and insufficiency are widespread on a global scale, with multiple factors playing a role in their development, such as limited exposure to sunlight, inadequate dietary consumption, as well as obesity and abdominal fat accumulation. Abdominal obesity, assessed with waist circumference (WC), is associated with metabolic syndrome and has been linked to low vitamin D levels. This study aimed to investigate the relationship between visceral adipose tissue (VAT) and vitamin D levels, particularly examining the potential threshold for vitamin D storage and sequestration using adipose tissue. The study was conducted between 2020 and 2022 with 58 patients from an internal medicine outpatient department. Patients with certain medical conditions and those taking medications affecting bone metabolism were excluded. Blood samples were collected at baseline and after 6 months of monthly cholecalciferol supplementation. Ultrasonography was used to evaluate adipose tissue measurements, including subcutaneous adipose tissue thickness, VAT, preperitoneal adipose tissue (PPAT), and prerenal adipose tissue (PRAT). Anthropometric measures such as the waist-to-hip ratio and waist-to-height ratio were also assessed. The results showed that all subjects had significant hypovitaminosis D at baseline. After 6 months of supplementation, the mean increase in vitamin D levels was 9.6 ng/mL, with 55.2% of subjects becoming deficient. The study revealed a significant correlation between follow-up vitamin D levels and waist circumference, hip circumference, and VAT. VAT exhibited a strong correlation not only with vitamin D levels but also with waist circumference. When analyzing gender differences, males showed a higher weight and waist-to-hip ratio, while females had higher body adiposity indexes and subcutaneous adipose tissue measurements. In conclusion, this study highlights the relationship between VAT and vitamin D levels, emphasizing the potential role of adipose tissue in vitamin D availability. Waist circumference was identified as a surrogate measure for VAT evaluation. Furthermore, the study showed variations in vitamin D response to supplementation between genders, with a higher percentage of males reaching normal vitamin D levels. Predictive factors for vitamin D levels differed between genders, with waist circumference being a significant predictor in males and body adiposity index in females.

Goishi tea leaf powder affects lower body weight and visceral fat accumulation during energy restriction in obese rats.

Goishi tea is a unique Japanese post-fermented tea produced in Kochi prefecture. The aim of this study was to investigate whether the supplementation of energy-restricted diet with Goishi tea leaves affects body weight, visceral fat accumulation, and fecal lipids in diet-induced obese rats. 18 male Wistar rats were fed a high-fat diet for 12 weeks. Subsequently, the diet-induced obese rats were fed a low-energy diet containing 1% (G1 group) or 3% (G3 group) of Goishi tea leaf powder, or without any tea extracts (C group) for 4 weeks. After 4 weeks, body weight and body fat ratio were significantly lower in the G3 group than in the C group. Plasma insulin levels were significantly higher in the C group than in the G1 and G3 groups, whereas plasma leptin levels were significantly lower in the G3 group than in the C group. In addition, the lipid absorption rate was significantly lower in the G3 group than in the C and G1 groups. In conclusion, the administration of Goishi tea leaves under dietary restrictions might contribute to body weight reduction and inhibition of lipid absorption, as a diet therapy to help prevent obesity and metabolic syndrome. J. Med. Invest. 70 : 60-65, February, 2023.

Omega-3-Supplemented Fat Diet Drives Immune Metabolic Response in Visceral Adipose Tissue by Modulating Gut Microbiota in a Mouse Model of Obesity.

Obesity is a chronic, relapsing, and multifactorial disease characterized by excessive accumulation of adipose tissue (AT), and is associated with inflammation mainly in white adipose tissue (WAT) and an increase in pro-inflammatory M1 macrophages and other immune cells. This milieu favors the secretion of cytokines and adipokines, contributing to AT dysfunction (ATD) and metabolic dysregulation. Numerous articles link specific changes in the gut microbiota (GM) to the development of obesity and its associated disorders, highlighting the role of diet, particularly fatty acid composition, in modulating the taxonomic profile. The aim of this study was to analyze the effect of a medium-fat-content diet (11%) supplemented with omega-3 fatty acids (D2) on the development of obesity, and on the composition of the GM compared with a control diet with a low fat content (4%) (D1) over a 6-month period. The effect of omega-3 supplementation on metabolic parameters and the modulation of the immunological microenvironment in visceral adipose tissue (VAT) was also evaluated. Six-weeks-old mice were adapted for two weeks and then divided into two groups of eight mice each: a control group D1 and the experimental group D2. Their body weight was recorded at 0, 4, 12, and 24 weeks post-differential feeding and stool samples were simultaneously collected to determine the GM composition. Four mice per group were sacrificed on week 24 and their VAT was taken to determine the immune cells phenotypes (M1 or M2 macrophages) and inflammatory biomarkers. Blood samples were used to determine the glucose, total LDL and HDL cholesterol LDL, HDL and total cholesterol, triglycerides, liver enzymes, leptin, and adiponectin. Body weight measurement showed significant differences at 4 (D1 = 32.0 ± 2.0 g vs. D2 = 36.2 ± 4.5 g, p-value = 0.0339), 12 (D1 = 35.7 ± 4.1 g vs. D2 = 45.3 ± 4.9 g, p-value = 0.0009), and 24 weeks (D1 = 37.5 ± 4.7 g vs. D2 = 47.9 ± 4.7, p-value = 0.0009). The effects of diet on the GM composition changed over time: in the first 12 weeks, α and ß diversity differed considerably according to diet and weight increase. In contrast, at 24 weeks, the composition, although still different between groups D1 and D2, showed changes compared with previous samples, suggesting the beneficial effects of omega-3 fatty acids in D2. With regard to metabolic analysis, the results did not reveal relevant changes in biomarkers in accordance with AT studies showing an anti-inflammatory environment and conserved structure and function, which is in contrast to reported findings for pathogenic obesity. In conclusion, the results suggest that the constant and sustained administration of omega-3 fatty acids induced specific changes in GM composition, mainly with increases in Lactobacillus and Ligilactobacillus species, which, in turn, modulated the immune metabolic response of AT in this mouse model of obesity.

Diet Supplementation of Luteolin before Fatty Liver Formation Improves Hepatic Steatosis in Obese Mice by Inhibiting Visceral Adipose Tissue Lipolysis.

SCOPE: Serotonin (5-HT)-induced visceral adipocyte lipolysis is essential for the development of obesity-related complications. Diet supplementation of luteolin prevents high-fat diet (HFD)-fed mice against obesity and associated fatty liver. However, independent of the body weight loss, whether dietary luteolin can substantially reduce hepatic steatosis remains unclear. METHODS AND RESULTS: In differentiated 3T3-L1 cells, 5-HT treatment promotes adipocyte lipolysis, while luteolin significantly inhibits 5-HT-induced lipolysis, Ca2+ -PKG cascade, and SIRT1/FoxO1/AMPKα signaling through binding to 5-HT receptor HTR2B. Further, 5-week-old mice are fed with an HFD for 16 weeks. At the 6th, 8th, or 10th weeks of HFD feeding, some mice are switched to a luteolin-containing HFD, respectively. In all HFD-fed mice, body weight gain and body component are unaffected by dietary luteolin. However, diet supplementation of luteolin at the 6th or 8th, rather than at the 10th weeks, alleviates hepatic steatosis. Meanwhile, dietary luteolin reduces epididymal adipose tissue (EAT) lipolysis, and represses the level of lipolytic enzyme, the expression of Htr2b, and the activation of PKG and SIRT1/FoxO1/AMPKα signaling in EAT. CONCLUSIONS: Diet supplementation of luteolin before the formation of fatty liver protects HFD-fed mice against ectopic lipid deposition in liver by inhibiting visceral adipocyte lipolysis.

Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class.

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 ± 0.58 kg/m2) or class 3 (n = 8; BMI 47.79 ± 1.52 kg/m2) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment.

Early-life dietary exposures mediate persistent shifts in the gut microbiome and visceral fat metabolism.

In utero dietary exposures are linked to the development of metabolic syndrome in adult offspring. These dietary exposures can potentially impact gut microbial composition and offspring metabolic health. Female BALB/c mice were administered a lard, lard + flaxseed oil, high sugar, or control diet 4 wk before mating, throughout mating, pregnancy, and lactation. Female offspring were offered low-fat control diet at weaning. Fecal 16S sequencing was performed. Untargeted metabolomics was performed on visceral adipose tissue (VAT) of adult female offspring. Immunohistochemistry was used to determine adipocyte size, VAT collagen deposition, and macrophage content. Hippurate was administered via weekly intraperitoneal injections to low-fat and high-fat diet-fed female mice and VAT fibrosis and collagen 1A (COL1A) were assessed by immunohistochemistry. Lard diet exposure was associated with elevated body and VAT weight and dysregulated glucose metabolism. Lard + flaxseed oil attenuated these effects. Lard diet exposures were associated with increased adipocyte diameter and VAT macrophage count. Lard + flaxseed oil reduced adipocyte diameter and fibrosis compared with the lard diet. Hippurate-associated bacteria were influenced by lard versus lard + flax exposures that persisted to adulthood. VAT hippurate was increased in lard + flaxseed oil compared with lard diet. Hippurate supplementation mitigated VAT fibrosis pathology. Maternal high-fat lard diet consumption resulted in long-term metabolic and gut microbiome programming in offspring, impacting VAT inflammation and fibrosis, and was associated with reduced VAT hippurate content. These traits were not observed in maternal high-fat lard + flaxseed oil diet-exposed offspring. Hippurate supplementation reduced VAT fibrosis. These data suggest that detrimental effects of early-life high-fat lard diet exposure can be attenuated by dietary omega-3 polyunsaturated fatty acid supplementation.

Aframomum melegueta Seed Extract with Standardized Content of 6-Paradol Reduces Visceral Fat and Enhances Energy Expenditure in Overweight Adults - A Randomized Double-Blind, Placebo-Controlled Clinical Study.

Purpose: Aframomum melegueta (grains of paradise) seeds have been demonstrated to possess thermogenic potential. However, it is necessary to validate the functional attributes of A. melegueta seed extract in human subjects. Methods: In a double-blind, placebo-controlled clinical trial design, we have examined the thermogenic effects of a standardized A. melegueta seed extract (AfperFit). A total of 70 overweight male and female subjects (BMI ≥25.0 to ≤30.0 kg/m2) aged 20-50 years were enrolled and administered with either 250 mg of AfperFit or placebo in capsule form twice daily for 12 weeks. The primary efficacy endpoints included energy expenditure (indirect calorimetry), body composition (dual-energy X-ray absorptiometry (DEXA)) and fat distribution (computed tomography (CT scan)), analyzed at baseline and after 12 weeks of treatment. The effect of intervention on the quality of life was examined using SF-12 questionnaire. Results: Consumption of AfperFit significantly increased the energy expenditure (p<0.01), visceral fat area (p<0.001) and visceral to subcutaneous fat ratio (p<0.01) compared to placebo group. Consequently, there was significant body weight loss and reduction in BMI of subjects in AfperFit group compared to placebo (p<0.01). The safety evaluation showed that biochemical and hematological parameters were in the normal range. Supplementation of AfperFit was well tolerated during the study and no adverse effects were observed. Conclusion: Overall, this study validates the health benefits of A. melegueta seed extract as fat burner and recommends its use as a functional ingredient to improve the quality of life and general health.

α-Linolenic acid rich-chia seed modulates visceral adipose tissue collagen deposition, lipolytic enzymes expression, insulin signaling and GLUT-4 levels in a diet-induced adiposity rodent model.

Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid-rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal -eWAT- and retroperitoneal -rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.

Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1.

Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased pro-inflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22 m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERα in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERα/ERß ratio in VAT, estrogen supplementation mainly worked through ERß, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.

The Crosstalk between Gut Microbiota, Intestinal Immunological Niche and Visceral Adipose Tissue as a New Model for the Pathogenesis of Metabolic and Inflammatory Diseases: The Paradigm of Type 2 Diabetes Mellitus.

Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions, such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides, produced in the gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides and it is involved in lipid and glucose metabolism, and some immune reactions, through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a pro-inflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is associated with specific patterns of GM alterations, an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to new, interesting therapeutic approaches.

The Beneficial Effects of Astaxanthin on Glucose Metabolism and Modified Low-Density Lipoprotein in Healthy Volunteers and Subjects with Prediabetes.

Astaxanthin (ASTX) is an antioxidant agent. Recently, its use has been focused on the prevention of diabetes and atherosclerosis. We examined the effects of astaxanthin supplementation for 12 weeks on glucose metabolism, glycemic control, insulin sensitivity, lipid profiles and anthropometric indices in healthy volunteers including subjects with prediabetes with a randomized, placebo-controlled trial. METHODS: We enrolled 53 subjects who met our inclusion criteria and administered them with 12 mg astaxanthin or a placebo once daily for 12 weeks. Subsequently, their HbA1c levels, lipid profiles and biochemical parameters were determined. The participants also underwent a 75 g oral glucose tolerance test (OGTT), vascular endothelial function test and measurement of the visceral fat area. RESULTS: After astaxanthin supplementation for 12 weeks, glucose levels after 120 min in a 75 g OGTT significantly decreased compared to those before supplementation. Furthermore, the levels of HbA1c (5.64 ± 0.33 vs. 5.57 ± 0.39%, p < 0.05), apo E (4.43 ± 1.29 vs. 4.13 ± 1.24 mg/dL, p < 0.05) and malondialdehyde-modified low-density lipoprotein (87.3 ± 28.6 vs. 76.3 ± 24.6 U/L, p < 0.05) were also reduced, whereas total cholesterol (TC), triglyceride (TG) and high-density lipoprotein-C (HDL-C) levels were unaltered. The Matuda index, which is one of the parameters of insulin resistance, was improved in the ASTX group compared to that before supplementation. CONCLUSIONS: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.

Athrixia phylicoides tea infusion (bushman tea) improves adipokine balance, glucose homeostasis and lipid parameters in a diet-induced metabolic syndrome rat model.

BACKGROUND: Central obesity and insulin resistance are associated with metabolic syndrome (MetS) which is aggravated by diet and sedentary lifestyle. Athrixia phylicoides (AP) is reported by rural communities to have medicinal benefits associated with MetS such as obesity and type 2 diabetes. This study was aimed to investigate the effects of AP on diet-induced MetS in Wistar rats to validate its ethnopharmacological use. METHODS: AP was profiled for phytochemicals by LC-MS. After induction of MetS with high energy diet (HED), 30 male rats were divided into five treatment groups (n = 6): normal diet control, HED control, HED + AP 50 mg/Kg BW, HED + AP 100 mg/Kg BW and HED + 50 mg/Kg BW metformin. The rats were treated daily for 8 weeks orally after which weight gain, visceral fat, total cholesterol, free fatty acids (FFAs) and adipokine regulation; leptin: adiponectin ratio (LAR) were assessed. Also, glucose homeostatic parameters including fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glucose transporter 4 (GLUT 4), insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. RESULTS: Findings showed that AP was rich in polyphenols. The HED control group showed derangements of the selected blood parameters of MetS. AP reversed diet-induced weight gain by reducing visceral fat, total blood cholesterol and circulating FFAs (p ≤ 0.05). Treatment with AP improved adipokine regulation depicted by reduced LAR (p<0.05). Treatment with AP improved parameters of glucose homeostasis as demonstrated by reduced FBG and HOMA-IR (p ≤ 0.05) and increased GLUT 4 (p<0.05). CONCLUSION: Athrixia phylicoides tea infusion was shown to possess anti-obesity and anti-inflammatory properties, improved glucose uptake and reduce insulin resistance in diet-induced MetS in rats which could be attributed to its richness in polyphenols. Therefore, AP could have potential benefits against type 2 diabetes and obesity which are components of MetS validating its ethnopharmacological use.

Preventive Effects of Green Tea Extract against Obesity Development in Zebrafish.

Various natural products (NPs) have been used to treat obesity and related diseases. However, the best way to fight obesity is preventive, with accurate body weight management through exercise, diet, or bioactive NPs to avoid obesity development. We demonstrated that green tea extract (GTE) is an anti-obesity NP using a zebrafish obesity model. Based on a hypothesis that GTE can prevent obesity, the objective of this study was to assess GTE's ability to attenuate obesity development. Juvenile zebrafish were pretreated with GTE for seven days before obesity induction via a high-fat diet; adult zebrafish were pretreated with GTE for two weeks before obesity induction by overfeeding. As a preventive intervention, GTE significantly decreased visceral adipose tissue accumulation in juveniles and ameliorated visceral adiposity and plasma triglyceride levels in adult zebrafish obesity models. RNA sequencing analysis was performed using liver tissues from adult obese zebrafish, with or without GTE administration, to investigate the underlying molecular mechanism. Transcriptome analysis revealed that preventive GTE treatment affects several pathways associated with anti-obesity regulation, including activation of STAT and downregulation of CEBP signaling pathways. In conclusion, GTE could be used as a preventive agent against obesity.

Tart Cherry Juice and Seeds Affect Pro-Inflammatory Markers in Visceral Adipose Tissue of High-Fat Diet Obese Rats.

BACKGROUND: Tart cherries (Prunus cerasus L.) are a rich source of anthocyanins. They are phytochemical flavonoids found in red and blue fruits, and vegetables that can reduce hyperlipidemia. Visceral Adipose Tissue (VAT) has emerged as a major player in driving obesity-related inflammatory response. METHODS: This study has investigated the potential positive effects of tart cherries on rats with Diet-Induced Obesity (DIO). In particular, the inflammatory status in retroperitoneal (RPW) and perigonadal (PGW) adipose tissue were studied. Rats were fed ad libitum for 17 weeks with a hypercaloric diet with the supplementation of tart cherries seeds powder (DS) and seeds powder plus tart cherries juice containing 1mg of anthocyanins (DJS). In RPW and PGW, expression of CRP, IL-1 ß, TNF-α, CCL2 and CD36, were measured by qRT-PCR, Western blot and immunohistochemistry techniques. RESULTS: No differences in the weight of RPW and PGW animals were found between DS and DJS groups compared to DIO rats. However, an increase of inflammatory markers was observed in DIO group in comparison with control lean rats. A modulation of these markers was evident upon tart cherry supplementation. CONCLUSION: Study results suggest that tart cherry enriched-diet did not modify the accumulation of visceral fat, but it decreased inflammatory markers in both tissues. Therefore, this supplementation could be useful, in combination with healthy lifestyles, to modify adipose tissue cell metabolism limiting-obesity related organ damage.

Fenofibrate Regulates Visceral Obesity and Nonalcoholic Steatohepatitis in Obese Female Ovariectomized C57BL/6J Mice.

Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, p < 0.05), visceral adipose tissue mass (-46%, p < 0.05), and visceral adipocyte size (-20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, p < 0.05) and infiltration of macrophages (-72%, p < 0.05), while concomitantly upregulating the expression of fatty acid ß-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice.

Palm oil consumption and its repercussion on endogenous fatty acids distribution.

The consumption of saturated lipids in combination with a sedentary lifestyle increases the risk of obesity and metabolic syndrome. However, the distribution of endogenous fatty acids (FA) after the consumption of saturated lipids and the connection between FA distribution and lipid metabolism-related genes relative expression have not been fully elucidated to date. In this study, we characterized FA profiles in the liver and visceral fats of Sprague Dawley (SD) rats fed with a high-palm-oil diet. The investigation showed that the levels of C16:0 and C18:1 (n-9) increased significantly (P < 0.05) in the liver of the high-palm-oil group (POG), while C16:1 (n-7) and C18:2 (n-6) accumulated markedly (P < 0.05) in the visceral fats of the control group (CN). A correlation analysis indicated a negative correlation between C16:0 and C16:1 (n-7) in the epididymal fat of POG. Our study also demonstrated that the intake of saturated lipids caused changes in lipid metabolism-related gene expression, especially stearoyl-CoA desaturase (SCD), which was upregulated at the third week but was inhibited in the subsequent weeks in the POG liver and perirenal fat. The SCD had a notable positive correlation with C16:1 (n-7) in the POG liver and perirenal fat but a significant negative correlation with C16:0 in the POG epididymal fat. In conclusion, the results of this study indicate that a high-C16:0 diet may result in adaptive SCD expression, and these findings may help to elucidate the effects of dietary fat on lipid metabolism.

Triterpene-enriched fractions from Eucalyptus tereticornis ameliorate metabolic alterations in a mouse model of diet-induced obesity.

ETNOPHARMACOLOGICAL RELEVANCE: Eucalyptus tereticornis Sm. (Eu) is a plant species used in traditional medicine to treat diabetes mellitus. Eu leaf extracts have been shown to regulate immuno-metabolic activities that are associated with obesity and insulin resistance. OBE100 and OBE104 are two natural Eu extracts that are rich in pentacyclic triterpenes. The major compounds identified in OBE100 are ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL), and the major compounds identified in OBE104 are UA and OA. AIM OF THE STUDY: This study aimed to investigate the effects of two extracts from Eu leaves with different triterpene composition in a nutritional animal model of prediabetes. METHODS: A mouse model of diet-induced obesity was used to analyze the effects of the OBE100 and OBE104 treatments on metabolic markers and gene expression in liver and visceral adipose tissue. RESULTS: Treating the prediabetic mouse model with OBE100 and OBE104 increased glucose tolerance. However, only the Eu extract that contained three triterpenes reduced mouse body weight, hepatic and adipose fat content, and plasma lipid levels. OBE100 treatment also led to decreased hepatic mRNA levels of PPARA, CPT1A, and SERBP1. In visceral adipose tissue, OBE100 treatment reduced expression of PPARA and ACACA and increased UCP1 expression. CONCLUSIONS: These results suggest that developing a new multitargeting bioactive compound from the natural extract from Eu may help combat obesity and diabetes. Treatment with OBE100 had better effects than OBE104 in a diet-induced obesity mouse model, suggesting that the OBE100 extract, which contains three triterpenes, may be beneficial in combating obesity.

Zinc Supplementation Decreases Obesity-Related Neuroinflammation and Improves Metabolic Function and Memory in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effects of zinc (Zn) supplementation on metabolic and neuroinflammatory parameters in cafeteria diet (CAF)-induced obesity in Wistar rats. METHODS: Animals were divided into four groups: control diet (CT); CT+Zn; CAF; CAF+Zn. The diet was administered for 20 weeks; Zn treatment (10 mg/kg/d) started at week 16 and it was conducted until the end of the diet protocol. Weight gain, visceral fat, and plasma levels of glucose, triglycerides, insulin, TNF-α, and IL-6, as well as homeostatic model assessment of insulin resistance, were assessed. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) expression in the cerebral cortex and toll-like receptor 4 (TLR-4) in the cerebral cortex and hippocampus were evaluated. Memory was assessed by the novel object recognition test. RESULTS: CAF diet increased weight gain, visceral fat, and plasma glucose, triglyceride, and TNF-α levels. Zn reversed the hyperglycemia caused by CAF diet and reduced IL-6 levels. In the cerebral cortex, GFAP was similar between groups; Iba-1 was increased by CAF diet but reduced in the CAF+Zn group. Zn reduced CAF-dependent TLR-4 increase in the hippocampus but not in the cerebral cortex. CAF-fed animals showed impaired recognition memory, whereas Zn reversed it. CONCLUSIONS: These findings demonstrate that Zn partially reverted obesity-related metabolic dysfunction and reduced neuroinflammation and memory deficit caused by CAF diet.

Pinto beans modulate the gut microbiome, augment MHC II protein, and antimicrobial peptide gene expression in mice fed a normal or western-style diet.

The onset of type 2 diabetes in obesity is associated with gut dysbiosis and a failure to confine commensal bacteria and toxins to the gut lumen while prebiotics may prevent these effects. This study evaluated the effects of pinto beans (PB) supplementation on cecal bacteria, short-chain fatty acids (SCFAs), distal ileal antigen presentation marker (major histocompatibility complex [MHC] II) and antimicrobial peptide genes during short-term high-fat, high sucrose (HFS) feeding. Six-week-old, male C57BL/6J mice were randomly assigned to four groups (n=12/group), and fed a control (C) or HFS diet with or without cooked PB (10%, wt/wt) for 30 days. Supplemental PB in both the C and HFS diets decreased the abundance of Tenericutes and the sulfate-reducing bacteria Bilophila. In contrast, PB raised the abundance of taxa within the SCFAs-producing family, Lachnospiraceae, compared to groups without PB. Consequently, fecal butyric acid was significantly higher in PB-supplemented groups compared to C and HFS groups. PB reversed the HFS-induced ablation of the distal ileal STAT3 phosphorylation, and up-regulated antimicrobial peptide genes (Reg3γ and Reg3ß). Furthermore, the expression of MHC II protein was elevated in the PB supplemented groups compared to C and HFS. Tenericutes and Bilophilia negatively correlated with activated STAT3 and MHC II proteins. Finally, supplemental PB improved fasting blood glucose, glucose tolerance and suppressed TNFα and inducible nitric oxide synthase mRNA in the visceral adipose tissue. Put together, the beneficial impact of PB supplementation on the gut may be central to its potential to protect against diet-induced inflammation and impaired glucose tolerance.