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.

Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity.

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.

Body Fat Distribution and Metabolic Changes in a Cohort of Adolescents Living With HIV Switched to an Antiretroviral Regimen Containing Dolutegravir.

Use of antiretrovirals is associated to body fat accumulation. We measured body composition in adolescents living with HIV switched to a dolutegravir-containing regimen. Trunk fat and trunk/body fat ratio markedly increased after 12 months. Total and low density lipoprotein cholesterol decreased after 3 months. Increase in trunk fat may put at risk of future cardiovascular problems, despite improvement in the lipid profile.

Lutein attenuates excessive lipid accumulation in differentiated 3T3-L1 cells and abdominal adipose tissue of rats by the SIRT1-mediated pathway.

OBJECTIVE: Obesity is now a worldwide disease and is mainly attributable to increased body fat deposition. In a growing number of epidemiological studies, lutein has been revealed to have different degrees of anti-obesity properties, but the potential underlying mechanisms that have been reported are limited. Therefore, we aimed to clarify the protective effects of lutein against excessive lipid accumulation, and we explored the role of SIRT1 and SIRT1-mediated pathways both in abdominal adipose tissue and mature 3T3-L1 cells during lutein administration. METHODS: In our design, male Sprague-Dawley rats were fed either control or high-fat diets with or without 25 mg/kg·bw/day lutein for 5 weeks. Additionally, differentiated 3T3-L1 cells were incubated with 40 µM lutein or 10 µM Ex527 for 24 h. RESULTS: Lutein supplementation decreased the body weight, abdominal fat index ratio, frequency and mean area of larger adipocytes in HE staining induced by the high-fat diet and then activated the expression of SIRT1 and thus upregulated FoxO1, ATGL, and HSL expression and downregulated SREBP-1, FAS, and ACC expression both in abdominal adipose tissue and differentiated 3T3-L1 cells. However, coincubation with Ex527 and lutein suppressed the activation of SIRT1 and reversed the expression of FoxO1, ATGL, HSL, SREBP-1, FAS, and ACC in comparison to those in the Lut group. CONCLUSIONS: Overall, we suggest that the effects of lutein on attenuating excessive lipid accumulation are dependent on the SIRT1-mediated pathway in vivo and in vitro, which indicates that lutein administration may be a potential strategy for preventing excessive lipid accumulation and obesity.

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet, but Not without Exercise Training.

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.

Adipose depot-specific effects of 16 weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial.

AIMS/HYPOTHESIS: In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity. METHODS: Forty-one healthy women with obesity (20 black; 21 white; 29 ± 6 years; BMI 32.0 ± 1.7 kg/m2; 44.0 ± 3.6% body fat) were randomised to consume 30 mg/day of pioglitazone (n = 21) or placebo (n = 20) for 16 weeks. SAS v9.4 was used to generate the block randomisation code sequence (stored in password-protected files) with a 1:1 allocation ratio. The participants and study staff involved in assessing and analysing data outcomes were blinded to the group assignments. The trial was conducted at Pennington Biomedical Research Center and ended in 2016. At baseline and post-intervention, subcutaneous abdominal (scABD) and femoral (scFEM) AT biopsies were collected, and in vivo cellular kinetics (primary endpoint of the trial) were assessed by an 8 week labelling protocol of deuterium (2H) into the DNA of adipose cells. Body composition was measured by dual-energy x-ray absorptiometry (DXA), scABD and visceral AT (VAT) by MRI, ectopic fat by 1H-MRS, and insulin sensitivity by an OGTT. RESULTS: After the 16 week intervention, there was a significant decrease in visceral fat (VAT:total abdominal AT [as a %]; p = 0.002) and an increase in the Matsuda index (i.e. improved insulin sensitivity; p = 0.04) in the pioglitazone group relative to the placebo group. A significant increase in the formation of new adipocytes was observed in the scFEM (Δ = 3.3 ± 1.6%; p = 0.04) but not the scABD depot (Δ = 2.0 ± 2.1%; p = 0.32) in the pioglitazone group relative to the placebo group. No serious adverse events were reported. CONCLUSIONS/INTERPRETATION: Pioglitazone may elicit distinct differences in in vivo adipogenesis in subcutaneous adipose depots in women with obesity, with increased rates in the protective scFEM. Trial registration ClinicalTrials.gov NCT01748994 Funding This study was funded by R01DK090607, P30DK072476, and R03DK112006 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health. The Robert C. and Veronica Atkins Foundation. Graphical abstract.

Effect of Overeating Dietary Protein at Different Levels on Circulating Lipids and Liver Lipid: The PROOF Study.

BACKGROUND: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. METHODS: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. RESULTS: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). CONCLUSIONS: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.

Dietary corn-resistant starch suppresses broiler abdominal fat deposition associated with the reduced cecal Firmicutes.

This study investigated the effects of dietary corn-resistant starch on lipid metabolism of broilers and its potential relationship with cecal microbiota modulation. A total of three hundred twenty 1-day-old male broilers were randomly assigned into 5 dietary treatments: 1 normal corn-soybean (NC) diet, 1 corn-soybean-based diet supplementation with 20% corn starch (CS), and 3 corn-soybean-based diets supplementation with 4, 8, and 12% corn resistant starch (RS) (identified as 4%RS, 8%RS, and 12%RS, respectively). Each group had 8 replicates with 8 broilers per replicate. The experiment lasted 21 d. The results showed that the abdominal fat percentage were lower in birds from 8%RS and 12%RS groups (0.75 and 0.58%, respectively) than those from NC and CS groups (1.20 and 1.28%, respectively; P < 0.05). The birds from 8%RS and 12%RS groups exhibited lower concentrations of blood triglyceride and nonestesterified fatty acid than those in the NC and CS groups (P < 0.05). Moreover, birds fed diets supplementation with 12% RS decreased the relative mRNA expressions of peroxisome proliferator-activated receptor gamma, ATP citrate-lyase, fatty acid synthase, and acetyl-CoA carboxylase in liver, and glycerol-3-phosphate acyltransferase in abdominal adipose tissue (P < 0.05). Microbiota analysis revealed that birds fed diets supplementation with 8 and 12% RS decreased the abundance of cecal Firmicutes by 23.08 and 20.47% and increased the proportion of Bacteroidetes by 24.33 and 21.92%, respectively, compared with the NC group (P < 0.05). In addition, correlation analysis revealed that many Firmicutes members had highly positive relationship with blood lipid levels and fat storage capacity, which might contribute to the lower abdominal fat phenotype. Overall, broilers receiving diets containing a higher concentration of RS harbor less Firmicutes, which decreased liver fatty acid synthesis and suppress abdominal fat deposition of birds during the starter phase. These findings provide a profound understanding about the relationship between gut microbial composition and lipid metabolism in broilers.

Quercetin Improving Lipid Metabolism by Regulating Lipid Metabolism Pathway of Ileum Mucosa in Broilers.

This study is aimed at evaluating the regulatory mechanism of quercetin on lipid metabolism in the ileum of broilers to better understand these pathways decreasing abdominal fat. 480 chickens were randomly divided into 4 groups (control, 0.02% quercetin, 0.04% quercetin, and 0.06% quercetin). Breast muscle, thigh muscle, and abdominal fat pad were removed and weighed at 42 d of age. Serum was obtained by centrifuging blood samples from the jugular vein (10 ml) to determine high-density lipoprotein (HDL), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), leptin, and adiponectin using ELISA. About 5 g of the ileum was harvested and immediately frozen in liquid nitrogen for RNA-seq. Then, the confirmation of RNA-seq results by the Real-Time Quantitative PCR (RT-qPCR) method was evaluated using Pearson's correlation. Compared with control, abdominal fat percentage was significantly decreased with increasing quercetin supplementation, and the best result was obtained at 0.06% dietary quercetin supplementation (P < 0.01). Breast muscle percentage was significantly decreased at 0.02% quercetin (P < 0.01), and thigh muscle percentage tended to increase (P = 0.078). Meanwhile, 0.04% and 0.06% quercetin significantly decreased TG (P < 0.01), TC (P < 0.01), and LDL content (P < 0.05) in serum. Serum leptin and adiponectin contents were significantly increased by 0.04% and 0.06% dietary quercetin supplementation, compared with the control (P < 0.01). Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to identify differently expressed genes and lipid metabolism pathways. Quercetin decreased abdominal fat percentage through regulating fat digestion and absorption, glycerophospholipid metabolism, AMPK signaling pathway, fatty acid degradation, and cholesterol metabolism.

Effects of bisphenol A at the safe reference dose on abdominal fat deposition in aged hens.

Bisphenol A (BPA) is an endocrine-disrupting chemical. Its influence on lipid homeostasis remains to be proven. In this study, the obese model of laying hens were induced using high-fat diet (HFD) to determine the lipid metabolism interference of BPA, especially its influence on estrogen receptors (ERs) and oxidative damage, at the dose of tolerable daily intake (TDI, 50 µg/kg body weight [BW]/day) and no observable adverse effect level (NOAEL, 5000 µg/kg BW/day). The results demonstrated that the TDI dose of BPA interacted with ERα more effectively than the NOAEL dose of BPA. The TDI dose of BPA increased the expression of ERα (esr1), which further changed the expression of lipid metabolism-related genes, such as cpt-1, lpl, creb1, and apov1. Furthermore, the abdominal fat rate, hematoxylin-eosin staining of adipocytes, and the average area of the hens were reduced. Therefore, the TDI dose of BPA played an estrogen-compensating role and weakened the effect of HFD on obesity in aged hens. By contrast, BPA at NOAEL dose exhibited great oxidative stress, which remarkably inhibited the activities of antioxidant-related enzymes (total superoxide dismutase and glutathione peroxidase) and promoted the excessive accumulation of lipid peroxidation products (malondialdehyde). Moreover, the increase in oxidative stress corresponded well with the increase in the expression of fat-forming genes (srebp-1, fas, acc, and ppar γ). That is, BPA at NOAEL may accelerate the process of fat formation.

Effects of the Non-Alcoholic Fraction of Beer on Abdominal Fat, Osteoporosis, and Body Hydration in Women.

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Anti-obesity Effect of Fermented Persimmon Extracts via Activation of AMP-Activated Protein Kinase.

There is significant cultivation of persimmon (Diospyros kaki) in East Asia, a plant whose fruit has abundant nutrients, including vitamins, polyphenols, and dietary fiber. Persimmon dietary supplements can benefit health by amelioration of diabetes, cardiovascular disease, and obesity. There are also persimmon-based beverages produced via fermentation, such as wines and vinegars, and increasing consumption of these products in East Asia. Although there is great interest in functional foods, the health effects of fermented persimmon extract (FPE) are completely unknown. We examined the effects of FPE on the metabolic parameters of mice fed a high-fat diet (HFD). Our results indicated that FPE supplementation led to an approx. 15% reduction of body weight, reduced abdominal and liver fat, and reduced serum levels of triglycerides, total cholesterol, and glucose. FPE also blocked the differentiation of murine 3T3-L1 pre-adipocyte cells into mature adipocytes. We suggest that gallic acid is a major bioactive component of FPE, and that AMP-activated protein kinase mediates the beneficial effects of FPE and gallic acid.

Short chain fatty acids could prevent fat deposition in pigs via regulating related hormones and genes.

Short chain fatty acids (SCFAs) are produced when indigestible carbohydrates, such as fiber and resistant starch, undergo fermentation by specific microbiota in the hindgut. This study was designed to investigate the effects of different SCFAs on the glucolipid metabolism and appetite regulation of pigs. In a 28-day experiment, 30 barrows were divided into five groups: (1) control, (2) 0.1% sodium acetate, (3) 0.1% sodium propionate, (4) 0.1% sodium butyrate, and (5) 0.1% mixed sodium SCFAs (in the ratio of 3 : 1 : 1, respectively). Acetate administration reduced the average daily feed intake and average daily body weight gain of pigs (P < 0.05), decreased serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-c) concentrations (P < 0.05), increased serum glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and leptin concentrations (P < 0.05), down-regulated fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c) mRNA expressions in the liver (P < 0.05), enhanced silent information regulator1 (SIRT1) mRNA expression in the longissimus dorsi (P < 0.05), and up-regulated free fatty acids receptor 2 (FFAR2) and PYY mRNA expressions in the colon (P < 0.05). Propionate administration also decreased serum TG, TC, and LDL-c concentrations (P < 0.05), increased serum GLP-1, PYY and leptin concentrations (P < 0.05), down-regulated glucose-6-phosphatase (G6PC) mRNA expression in the liver (P < 0.05), enhanced PPARγ coactivator-1α (PGC-1α) mRNA expression in the liver (P < 0.05), stimulated SIRT1 mRNA expression in the longissimus dorsi (P < 0.05), and up-regulated G6PC and glucagon mRNA expressions in the colon (P < 0.05). Butyrate administration down-regulated G6PC mRNA expression in the liver (P < 0.05), enhanced PGC-1α mRNA expression in the liver (P < 0.05), and increased lipase hormone-sensitive (LIPE) and carnitine palmitoyltransferase-1α (CPT-1α) mRNA expressions in the longissimus dorsi (P < 0.05). Overall, these results suggested that SCFAs could reduce lipogenesis, and enhance lipolysis in different tissues of pigs via regulating related hormones and genes, which would further illustrate the mechanisms underlying the beneficial effects of SCFAs on appetite and body weight control.

Effect of dietary inclusion of lecithin with choline on physiological stress of serum cholesterol fractions and enzymes, abdominal fat, growth performance, and mortality parameters of broiler chickens.

A total of 270 one-d-old Ross 308 broiler chicks were randomly allotted to 9 experimental diets (3 replicates of 10 birds each), including three types of supplemental lipotropic factors (control, 0.1% or 0.2% choline and 0.5% or 1% lecithin) in a 3 × 3 factorial arrangement. Supplementation of lecithin improved FCR values during 1-21 days of age. Although no differences were noticed for mortality index among different diets, the group supplemented with a combination of choline (0.1) and lecithin (0.5) showed the highest (P < 0.0001) production index. Choline (0.1% or 0.2%) significantly decreased serum total cholesterol by 11%, triglycerides by 21%, low-density lipoprotein (LDL) by 20%, and very low-density lipoprotein (VLDL) by 20%, while increased the glucose and high-density lipoprotein (HDL) values by 11% and 6%, respectively. On the other hand, lecithin significantly increased glucose, total cholesterol, triglycerides, HDL, LDL and VLDL by 4%, 9%, 7%, 24%, and 25%, respectively. Choline supplementation decreased the aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (AP); however, the lecithin addition increased their respective proportions. This study concluded that the combinations of 0.1% choline and 0.5% lecithin is the best among all other treatments because of the highest production index and least mortality.

Effect of Steamed Onion (ONIRO) Consumption on Body Fat and Metabolic Profiles in Overweight Subjects: A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: The aim of the study is to investigate the effect of Jeju steamed onion (ONIRO) on body fat and metabolic profiles in overweight subjects.Methods: This randomized, double-blind, placebo-controlled clinical intervention was conducted and completed at one clinical research site. The subjects (n = 70) were randomly divided into placebo or test group and were instructed to take before each meal either the placebo or ONIRO capsule for 12 weeks. Anthropometric as well as serum and metabolic parameters, including triglycerides, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, leptin, adiponectin, C-peptide, and aspartate aminotransferase (AST) were measured at baseline and after 12 weeks. Body composition was also measured by dual-energy x-ray absorptiometry (DEXA) and computed tomography (CT). This trial is registered under the trial registration code clinicaltrials.gov: NCT03645382 (https://register.clinicaltrials.gov).Results: Compared to the placebo, ONIRO supplementation for significantly reduced the percentage of body fat and fat mass as measured by DEXA (p = 0.028 and 0.022, respectively) with no significant effects on lean body mass. CT analyses at the L1 level showed a significant decrease in the areas of whole fat, visceral fat, and subcutaneous fat (p = 0.009, p = 0.039, p = 0.020, respectively), while CT scan of L4 resulted in a significant reduction of whole fat area and subcutaneous area (p = 0.006 and p = 0.012, respectively). The levels of triglycerides (TG) and C-peptide were significantly lower after 12 weeks of ONIRO treatment.Conclusions: These findings suggest that ONIRO supplementation reduces total body fat, notably abdominal visceral fat, with positive changes of the clinically relevant metabolic parameters serum TG and C-peptide.

The adiponectin receptor agonist AdipoRon normalizes glucose metabolism and prevents obesity but not growth retardation induced by glucocorticoids in young mice.

OBJECTIVE: Glucocorticoids (GCs) are highly effective anti-inflammatory and immunosuppressive drugs. However, prolonged GC therapy may cause numerous adverse effects leading to diabetes and obesity, as well as bone disorders such as osteoporosis in adults and growth retardation in children and adolescents. Prevention and care of the GC-induced adverse effects remain challenging. We have previously demonstrated the efficacy of a treatment with a non-peptidic agonist of adiponectin receptors, AdipoRon, to reverse behaviour disorders and fat mass gain induced by long-term GC treatment. In this work, we have established a relevant model of GC-induced growth and metabolic disorders and determined that AdipoRon is a potential therapeutic tool to reverse these metabolic disturbances. METHODS: 5-Week-old mice were treated continuously with or without corticosterone (35 mg/L) in drinking water for seven consecutive weeks. Taking advantage of this mouse model displaying various growth and metabolic disorders, we assayed whether AdipoRon (daily intraperitoneal injection of 1 mg/kg/day for the last 20 days) might prevent the GC-induced adverse effects. The control group was treated with vehicle only. Nutritional behaviors and metabolic parameters were followed-up throughout the treatment. Serum insulin and leptin levels were measured by ELISA. Computed tomography and histological analysis of adipose tissue were assessed at the end of the experimental procedure. RESULTS: We found that GC treatment in young mice resulted in continuously increased body weight gain associated with a food intake increase. Compared to vehicle-, GC-treated mice displayed early major hyperleptinemia (up to 6-fold more) and hyperinsulinemia (up to 20-fold more) maintained throughout the treatment. At the end of the experimental procedure, GC-treated mice displayed bone growth retardation (e.g. femur length 15.1 versus 14.0 mm, P < 0.01), higher abdominal adipose tissue volume (4.1 versus 2.3, P < 0.01) and altered glucose metabolism compared to control mice. Interestingly, AdipoRon prevented GC-induced effects on energy metabolism such as abdominal adiposity, insulinemia and leptinemia. However, AdipoRon failed to counteract bone growth retardation. CONCLUSION: We characterized the very early pathological steps induced by long-term GC in young mice in a relevant model, including growth retardation, fat mass gain and glucose homeostasis dysregulation. The adiponectin system stimulation enabled normalization of the adipose tissue and metabolic features of GC-treated mice. Adiponectin receptor agonists such as AdipoRon might constitute a novel way to counteract some GC-induced adverse effects.

Vitamin D release across abdominal adipose tissue in lean and obese men: The effect of ß-adrenergic stimulation.

Obesity is characterized by a blunted lipolytic response in abdominal subcutaneous adipose tissue (SAT) and low circulating vitamin D levels. Here we investigated whether an impaired SAT lipolytic response coincides with an impaired SAT vitamin D release in eight lean and six obese men. 25-hydroxyvitamin D3 [25(OH)D3 ] and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] fluxes across SAT were measured using arterio-venous blood sampling in combination with AT blood flow measurements after an overnight fast and during 1-hr intravenous infusion of the non-selective ß-adrenergic agonist isoprenaline (20 ng·kg FFM-1 ·min-1 ). 1,25(OH)2 D3 was released across abdominal SAT during isoprenaline infusion in lean [-0.01 (-0.04 to 0.00) pmol*100 g tissue-1 *min-1 , p = .017 vs. zero flux], but not in obese men [0.01 (0.00 to 0.02) pmol*100 g tissue-1 *min-1 , p = .116 vs. zero flux], and accompanied by an impaired isoprenaline-induced lipolytic response in abdominal SAT of obese versus lean men. Isoprenaline had no significant effects on net 25(OH)D3 release across abdominal SAT and plasma vitamin D metabolites in lean and obese men. To conclude, a blunted isoprenaline-mediated lipolysis is accompanied by reduced release of 1,25(OH)2 D3 vitamin D across abdominal SAT in obesity.

Heated egg white has no effect, but lactic fermented and unheated egg white reduces abdominal fat in rats.

BACKGROUND: We previously reported the abdominal fat-reducing effect of unheated egg white proteins (EWP); however, unheated egg white is actually rarely consumed. We thus investigated the effect of heated egg white on abdominal fat in rats. METHODS: Male SD rats were divided into two groups that were allowed to consume different dietary preparations containing casein or heated egg white for 4 weeks (Trial 1). We studied whether a heated form and a lactic fermented form of egg white (FLE) are as effective as unheated egg white for reducing abdominal fat. For this, we divided male SD rats into four groups that were allowed to consume different dietary preparations containing casein, unheated egg white, heated egg white, or lactic fermented egg white for 4 weeks (Trial 2). RESULTS: Animals in the heated egg white group showed no significant difference in abdominal fat weight compared with those in the casein group (Trial 1). Animals in the unheated egg white group and the FLE group had significantly lower levels of abdominal fat weight than those in the casein group (Trial 2). Ovalbumin in heated egg white was degraded by pepsin, whereas ovalbumin in unheated egg white and lactic acid fermented egg white was not degraded appreciably by pepsin. It was reported that EWP inhibit triglyceride absorption in rat. In the present study, EWP pepsin hydrolysate inhibited the micellar solubility of fatty acids in vitro. In particular, ovalbumin inhibited the micellar solubility of fatty acids. CONCLUSIONS: These results indicate that lactic fermented egg white reduces visceral fat in rats and suggest that different levels of susceptibility of ovalbumin to pepsin digestion underlie the varying effectiveness among the egg white preparations.

Effects of second-generation antipsychotics on human subcutaneous adipose tissue metabolism.

OBJECTIVE: Metabolic syndrome is prevalent in up to 50% of schizophrenia patients, which reduces their quality of life and their compliance with the treatment. It is unclear whether metabolic adverse effects of these agents are due to their direct effect on insulin-sensitive tissues or are secondary to increased adiposity. The study aimed to investigate the direct effects of the second-generation antipsychotics olanzapine and aripiprazole on human subcutaneous adipose tissue and isolated adipocyte metabolism. METHODS: Abdominal subcutaneous adipose tissue needle biopsies were taken from 72 healthy subjects (49 F/23 M; age: 19-78 yr; BMI: 20.0-35.6 kg/m2). Isolated adipocytes or adipose tissue were respectively pre-incubated short- (30 min) and long-term (24 h, 72 h) with or without olanzapine (0.004 µM - 20 µM) and aripiprazole (0.002 µM - 100 µM). Pre-incubated adipose tissue was then snap-frozen for mRNA expression analysis of adipokines genes and genes involved in inflammation, adipogenesis, and mitochondrial function. Isolated adipocytes were used to measure basal and insulin-stimulated glucose uptake and lipolysis. RESULTS: Acute treatment with a therapeutic concentration of olanzapine decreases basal lipolysis in isolated adipocytes; this effect was not observed after long-term incubation with the drug. Supra-therapeutic concentration of aripiprazole reduced basal and insulin-stimulated glucose uptake after short- and long-term pre-incubation. Both drugs at supra-therapeutic concentrations downregulated the expression of the pro-inflammatory cytokines IL6 and IL1B genes after 72 h incubation. Similarly, supra-therapeutic concentrations of both drugs and therapeutic concentration of olanzapine, reduced the expression of PPARGC1A, PDK4, and CPT1B genes involved in the regulation of mitochondrial functions. Neither of the antipsychotics affected the expression of the main adipokines LEP and ADIPOQ, genes involved in the regulation of lipid metabolism, LPL and FASN, nor the master adipogenesis regulator, PPARG. CONCLUSION: Therapheutic concentrations of olanzapine and aripiprazole have a moderate direct effect on adipocyte lipid and glucose metabolism, respectively. At supra-therapeutic concentrations, both of the antipsychotics seem to act as anti-inflammatory agents and mildly suppressed genes involved in the regulation of mitochondrial functions, which could potentially contribute to metabolic adverse effects. Alternatively, second-generation antipsychotics could induce metabolic side effects via acting on other insulin-sensitive tissues and central nervous system.

The effects of Pandanus amaryllifolius (Roxb.) leaf water extracts on fructose-induced metabolic syndrome rat model.

BACKGROUND: Metabolic syndrome is a non-communicable disease inclusive of risk factors such as central obesity, hypertension, hyperglycaemia and dyslipidaemia. In this present study, we investigated the ability of Pandanus amaryllifolius (PA) leaf water extract to reverse the cluster of diseases in an established rat model induced by fructose in drinking water. METHODS: Thirty healthy adult male Wistar rats (150-180 g) were randomly divided into three groups which included control (C; n = 6), PA extract (PAE; n = 6) and Metabolic Syndrome (MetS; n = 18). Food and fluid were given ad libitum for 8 weeks. These groups differed in fluid intake whereby rats received tap water, 10% of PA leaf water extracts and 20% of fructose in drinking water in group C, PAE and MetS, respectively. After 8 weeks, the MetS group was further subdivided into three subgroups namely MetS1 (n = 6), MetS2 (n = 6) and MetS3 (n = 6). The C, PAE and MetS1 were sacrificed. MetS1 group was sacrificed as the control for metabolic syndrome. MetS2 and MetS3 groups were treated with only tap water and 10% of PA leaf water extract respectively for another 8 weeks. The parameters for physiological and metabolic changes such as obesity, hypertension, hyperglycaemia, dyslipidaemia, and inflammatory biomarkers (NFκß p65, TNFα, leptin and adiponectin) were measured. RESULTS: The intake of 20% of fructose in drinking water induced full blown of metabolic syndrome symptoms, including obesity, hypertension, dyslipidaemia and hyperglycaemia in male Wistar rats. Subsequently, treatment with PA leaf water extract improved obesity parameters including BMI, abdominal adipose tissue deposition and adipocytes size, systolic and diastolic blood pressures, fasting plasma glucose, triglycerides, high density lipoprotein with neutral effects on inflammatory biomarkers. CONCLUSIONS: Administration of PA in metabolic syndrome rat model attenuates most of the metabolic syndrome symptoms as well as improves obesity. Therefore, PA which is rich in total flavonoids and total phenolic acids can be suggested as a useful dietary supplement to improve metabolic syndrome components induces by fructose.