Anti-Obesity and Antidiabetic Effects of Nelumbinis Semen Powder in High-Fat Diet-Induced Obese C57BL/6 Mice

Nelumbinis Semen (NS, the seeds of Nelumbo nucifera) extract is a traditional Korean medicine with anti-oxidant activity. The present study examined the anti-obesity and antidiabetic effects of NS powder in high-fat diet (HFD)-induced obese C57BL/6 mice. Mice (n = 8/group) were fed a normal diet (CON), HFD, HFD containing 5% NS powder (HFD-NS5%), or HFD containing 10% NS powder (HFD-NS10%) for 12 weeks. Food intake was relatively higher in groups HFD-NS5% and HFD-NS10%, while the food efficiency ratio was highest in group HFD (p < 0.05). HFD-NS5% reduced the body weight (−39.1%) and fat weight (−26.6%), including epididymal fat and perirenal fat, and lowered the serum triglyceride levels (−20.6%) compared with HFD. Groups HFD-NS5% and HFD-NS10% showed hepatoprotective properties, reducing the serum ALT levels (p < 0.05) and fat globules (size and number) in the liver compared with group HFD. HFD-NS5% and HFD-NS10% regulated the blood glucose, improved the glucose intolerance, and showed a 12.5% and 15.0% reduction in the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT), and a 26.8% and 47.3% improvement in homeostatic model assessment insulin resistance (HOMA-IR), respectively, compared with HFD (p < 0.05). Regarding the expressions of genes related to anti-obesity and antidiabetes, there was a 1.7- and 1.3-fold increase in PPAR-α protein expression, 1.4- and 1.6-fold increase in PPAR-γ protein expression, and 0.7- and 0.6-fold decrease in TNF-α protein expression, respectively, following HFD-NS5% and HFD-NS10% treatments, compared with HFD, and GLUT4 protein expression increased relative to CON (p < 0.05). These results comprehensively provide the fundamental data for NS powder’s functional and health-promoting benefits associated with anti-obesity and antidiabetes.     

Selenium Deficiency during Pregnancy in Mice Impairs Exercise Performance and Metabolic Function in Adult Offspring

Selenium deficiency during the perinatal period programs metabolic dysfunction in offspring. Postnatal exercise may prevent the development of programmed metabolic disease. This study investigated the impact of selenium deficiency on offspring exercise behavior and whether this improved metabolic health. Female C57BL/6 mice were randomly allocated to control (NormalSe, >190 μg/Se/kg, n = 8) or low-selenium (LowSe, <50 μg/Se/kg, n = 8) diets from four weeks before mating. Male offspring were weaned at postnatal day (PN) twenty-four and placed on a normal chow diet. At PN60, mice were placed in cages with bi-directional running wheels and monitored until PN180. LowSe offspring had a reduced average weekly running speed and distance (p < 0.05). LowSe offspring exhibited glucose intolerance, with increased peak blood glucose (p < 0.05) and area under the curve following an intra-peritoneal injection of glucose (p < 0.05). Furthermore, mRNA expression of several selenoproteins within cardiac and skeletal muscle were increased in LowSe offspring (p < 0.05). The results indicated that selenium deficiency during development reduces exercise behavior. Furthermore, exercise does not prevent programmed glucose intolerance in low-selenium offspring. This highlights that exercise may not be the optimal intervention for metabolic disease in offspring impacted by selenium deficiency in early life.     

Ergogenic Effects of Green Tea Combined with Isolated Soy Protein on Increasing Muscle Mass and Exercise Performance in Resistance-Trained Mice

It is well known that supplementation with high protein after exercise can effectively promote muscle synthesis and repair, while green tea is rich in catechins that have antioxidant effects. We aimed to explore the effects of green tea combined with isolated soy protein on increase muscle mass in resistance-trained mice. A total of 32 male ICR mice (8-weeks old) were divided into four groups (n = 8/group), sedentary control group (SC), isolated soy protein with green tea group (ISPG), resistance training group (RT), isolated soy protein and green tea combine with resistance training group (ISPG + RT). All mice received control or ISPG by oral gavage for four consecutive weeks. Forelimb grip and exhaustive swimming time were used for exercise performance evaluation. In biochemical profile, we analyzed lactate, ammonia, blood urea nitrogen (BUN), and glucose and muscle damage index creatine kinase (CK) after exercise as biochemical parameters of exercise fatigue. The grip strength, muscular endurance, and exhaustive swimming time of the ISPG + RT group were significantly increased than other groups (p < 0.05), and also significantly decreased in serum lactate and ammonia levels (p < 0.05, respectively). The ISP + RT group was not only increased in quadriceps weight, (p < 0.05) but also decreased EFP (p < 0.05). We recommend using a 4-week supplementation with ISPG, combined with RT, to increase muscle mass, exercise performance, glycogen storage, and reduce fatigue biochemical parameters after exercise. The benefits of long-term supplementation or application to human supplementation can be further explored in the future.     

Therapeutic Effects of Morinda citrifolia Linn. (Noni) Aqueous Fruit Extract on the Glucose and Lipid Metabolism in High-Fat/High-Fructose-Fed Swiss Mice

The aim of this study was to evaluate the therapeutic effects of two different doses (250 and 500 mg/kg) of Morinda citrifolia fruit aqueous extract (AE) in high-fat/high-fructose-fed Swiss mice. The food intake, body weight, serum biochemical, oral glucose tolerance test (OGTT), and enzyme-linked immunosorbent assay (ELISA), as well as histological analyses of the liver, pancreatic, and epididymal adipose tissue, were used to determine the biochemical and histological parameters. The chemical profile of the extract was determined by ultra-fast liquid chromatography–diode array detector–tandem mass spectrometry (UFLC–DAD–MS), and quantitative real-time PCR (qRT-PCR) was used to evaluate the gene expressions involved in the lipid and glucose metabolism, such as peroxisome proliferative-activated receptors-γ (PPAR-γ), -α (PPAR-α), fatty acid synthase (FAS), glucose-6-phosphatase (G6P), sterol regulatory binding protein-1c (SREBP-1c), carbohydrate-responsive element-binding protein (ChREBP), and fetuin-A. Seventeen compounds were tentatively identified, including iridoids, noniosides, and the flavonoid rutin. The higher dose of AE (AE 500 mg/kg) was demonstrated to improve the glucose tolerance; however, both doses did not have effects on the other metabolic and histological parameters. AE at 500 mg/kg downregulated the PPAR-γ, SREBP-1c, and fetuin-A mRNA in the liver and upregulated the PPAR-α mRNA in white adipose tissue, suggesting that the hypoglycemic effects could be associated with the expression of genes involved in de novo lipogenesis.     

Association between Adipose Tissue Depots and Dyslipidemia: The KORA-MRI Population-Based Study

Obesity increases the risk of cardiovascular diseases (CVD), however, whether adipose tissue relates to dyslipidemia, and consequently to cardiovascular events remains unknown. Thus, we investigated the association of adipose tissue with circulating lipoproteins and triglycerides (TG) in subjects without CVD. 384 participants from the KORA-MRI study (mean age 56.2 ± 9.2 years; 41.9% female) underwent whole-body 3T-MRI. Visceral (VAT) and subcutaneous adipose tissue (SAT) derived from T1-DIXON-sequence using a semi-automatic algorithm. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and TG were measured. Linear regression was applied to examine the relationships between adipose tissue, circulating lipoproteins, and TG, adjusting for risk factors. VAT was associated with total cholesterol (per SD increase) (ß = 0.39, p < 0.001). Total adipose tissue (TAT) and VAT were inversely associated with HDL (ß = −0.09, p = 0.009; ß = −0.14, p < 0.001), and positively associated with LDL (ß = 0.32, p < 0.001; ß = 0.37, p < 0.001). All adipose tissues were associated with TG (ß = 0.20, p < 0.001; ß = 0.27, p < 0.001; ß = 0.11, p = 0.004). Stratified analysis by sex and body mass index (BMI) was confirmatory in women and in individuals with BMI < 30. Our results suggest that adipose tissue plays an important role in increasing CVD risk independent of BMI, whereas gender imbalance may be explained by accurate characterization and quantification of adipose tissue.     

Evaluating Anticancer and Immunomodulatory Effects of Spirulina (Arthrospira) platensis and Gamma-Tocotrienol Supplementation in a Syngeneic Mouse Model of Breast Cancer

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and Spirulina, were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed Spirulina, γT3, or a combination of Spirulina and γT3 (Spirulina + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction (p < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + Spirulina. There was a marked increase (p < 0.05) of CD4/CD127⁺ T-cells and decrease (p < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or Spirulina. The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase (p < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant (p > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + Spirulina treatment did not show any synergistic anticancer effects in this study model.     

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.     

Differential Effects of Short-Chain Fatty Acids on L6 Myotube Inflammatory Mediator Production in Response to Lipopolysaccharide- or Palmitic Acid-Stimulation

Short-chain fatty acids (SCFA) produced from dietary non-digestible carbohydrate fermentation have metabolic effects in skeletal muscle; however, their effect on inflammatory mediator production is unknown. In this study, L6 myotubes were cultured with individual SCFA (acetate, propionate, and butyrate) at 0.5 mM and 2.5 mM ± 10 ng/mL lipopolysaccharide (LPS) or ± 500 µM palmitic acid (PA) for 24 h. In response to LPS, only butyrate had an effect at the lower concentration (0.5 mM), whereas at the higher concentration (2.5 mM) both propionate and butyrate reduced MCP-1, MIP-1α, and RANTES secretion (p < 0.05), and only butyrate reduced IL-6 secretion and intracellular protein levels of phospho-STAT3 (p < 0.05). In response to PA, 0.5 mM butyrate reduced protein expression of phospho-NFκB p65 and the secretion of IL-6, MIP-1α, and MCP-1, whereas all three SCFA reduced RANTES secretion (p < 0.05). At the 2.5 mM SCFA concentration combined with PA stimulation, all three SCFA reduced intracellular protein expression of phospho-NFκB p65 and phospho-STAT3 and secreted protein levels of MCP-1, IL-6, and RANTES, whereas only butyrate reduced secretion of MIP-1α (p < 0.05). Thus, SCFA exhibit differential effects on inflammatory mediator expression in response to LPS and PA stimulation, which has implications for their individual impacts on inflammation-mediated skeletal muscle dysfunction.     

Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice

Objective

This study investigated the effects of indole-3-carbinol (I3C), a cruciferous vegetable derivative, on obesity and its associated factors in high-fat-diet-induced obese (DIO) mice.

Methods

Eighteen male C57BL/6 mice were randomly assigned to one of three groups: basal, high fat (HF), and HF + 5 mg/kg of I3C intraperitoneally (HFI). After 12 wk of treatment, obesity-associated factors, including body weight, organ weight, serum concentrations of glucose, triacylglycerol, insulin, and adipokines, and macrophage accumulation and lipid metabolism-associated factors in epididymal adipose tissue were measured.

Results

Body weight and epididymal adipose tissue weight were greater (P < 0.01), and adipocytes were larger in the HF group than in the basal and HFI groups. Compared with the HF group, the HFI group had improved glucose tolerance, a higher serum adiponectin concentration, lower serum glucose, triacylglycerol, insulin, and leptin concentrations, and less F4/80 expression in epididymal adipose tissue (P < 0.001). Furthermore, I3C treatment decreased acetyl coenzyme A carboxylase mRNA expression (P < 0.05) and increased peroxisome proliferator-activated receptor-γ protein expression (P < 0.05) in epididymal adipose tissue of DIO mice.

Conclusion

The I3C treatment decreased body weight and fat accumulation and infiltrated macrophages in epididymal adipose tissue of DIO mice, and these reductions were associated with improved glucose tolerance and with modulated expression of adipokines and lipogenic-associated gene products, including acetyl coenzyme A carboxylase and peroxisome proliferator-activated receptor-γ.     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Cholesterol-induced inflammation and macrophage accumulation in adipose tissue is reduced by a low carbohydrate diet in guinea pigs

BACKGROUND/OBJECTIVES

The main objective of this study was to evaluate the effects of a high cholesterol (HC) dietary challenge on cholesterol tissue accumulation, inflammation, adipocyte differentiation, and macrophage infiltration in guinea pigs. A second objective was to assess whether macronutrient manipulation would reverse these metabolic alterations.

MATERIALS/METHODS

Male Hartley guinea pigs (10/group) were assigned to either low cholesterol (LC) (0.04g/100g) or high cholesterol (HC) (0.25g/100g) diets for six weeks. For the second experiment, 20 guinea pigs were fed the HC diet for six weeks and then assigned to either a low carbohydrate (CHO) diet (L-CHO) (10% energy from CHO) or a high CHO diet (H-CHO) (54% CHO) for an additional six weeks.

RESULTS

Higher concentrations of total (P < 0.005) and free (P < 0.05) cholesterol were observed in both adipose tissue and aortas of guinea pigs fed the HC compared to those in the LC group. In addition, higher concentrations of pro-inflammatory cytokines in the adipose tissue (P < 0.005) and lower concentrations of anti-inflammatory interleukin (IL)-10 were observed in the HC group (P < 0.05) compared to the LC group. Of particular interest, adipocytes in the HC group were smaller in size (P < 0.05) and showed increased macrophage infiltration compared to the LC group. When compared to the H-CHO group, lower concentrations of cholesterol in both adipose and aortas as well as lower concentrations of inflammatory cytokines in adipose tissue were observed in the L-CHO group (P < 0.05). In addition, guinea pigs fed the L-CHO exhibited larger adipose cells and lower macrophage infiltration compared to the H-CHO group.

CONCLUSIONS

The results of this study strongly suggest that HC induces metabolic dysregulation associated with inflammation in adipose tissue and that L-CHO is more effective than H-CHO in attenuating these detrimental effects.     

Circulating SIRT1 and Sclerostin Correlates with Bone Status in Young Women with Different Degrees of Adiposity

Sirtuin1 (SIRT1) and sclerostin play important roles in adipose tissue and bone metabolism. We evaluated the circulating SIRT1 and sclerostin relationship with mass and quality of bone while considering the degree of adiposity. Sixty-six premenopausal women (16 underweight, 25 normal weight and 25 with obesity), aged <50 years, were enrolled. Plasma SIRT1, sclerostin and DXA body composition (total fat mass (FM), abdominal visceral adipose tissue, lean mass, trabecular bone score (TBS) and lumbar spine and femoral neck (FN) bone mineral density (BMD)) were assessed. The patients with obesity showed the lowest SIRT1 and TBS values and the highest sclerostin concentrations; BMD increased with FM and BMI and had an inverse association with SIRT1. Sclerostin was negatively correlated with SIRT1 (ρ = −0.37, p = 0.002). When spine BMD, FN BMD and TBS were standardized for BMI, a positive correlation with SIRT1 and a negative correlation with sclerostin were seen (p < 0.005). In the regression analysis, sclerostin was the best independent, negative predictor for BMD and TBS, while SIRT1 directly predicted TBS (p < 0.05). In conclusion, blood measurement of SIRT1 and sclerostin could represent a snapshot of the bone status that, taking into account the degree of adiposity, may reduce the interference of confounding factors in the interpretation of bone health parameters.     

β-Lactoglobulin Elevates Insulin and Glucagon Concentrations Compared with Whey Protein—A Randomized Double-Blinded Crossover Trial in Patients with Type Two Diabetes Mellitus

Whey protein is an insulinotropic fraction of dairy that reduces postprandial glucose levels in patients with type 2 diabetes mellitus (T2DM). We have recently shown that β-lactoglobulin (BLG), the largest protein fraction of whey, elevates insulin concentrations compared with iso-nitrogenous whey protein isolate (WPI) in healthy individuals. We therefore hypothesized that BLG pre-meals would lower glucose levels compared with WPI in patients with T2DM. We investigated 16 participants with T2DM using a randomized double-blinded cross-over design with two pre-meal interventions, (i) 25 g BLG and (ii) 25 g WPI prior to an oral glucose tolerance test (OGTT), followed by four days of continuous glucose monitoring (CGM) at home. BLG increased concentrations of insulin with 10%, glucagon with 20%, and glucose with 10% compared with WPI after the OGTT (all p < 0.05). Both BLG and WPI reduced the interstitial fluid (ISF) glucose concentrations (using CGM) with 2 mM and lowered glycemic variability with 10–15%, compared with tap-water (p < 0.05), and WPI lowered the ISF glucose with 0.5 mM compared with BLG from 120 min and onwards (p < 0.05). In conclusion, BLG pre-meals resulted in higher insulin, glucagon, and glucose concentrations compared with WPI in participants with T2DM. Pre-meal servings of WPI remains the most potent protein in terms of lowering postprandial glucose excursions.     

Navy Bean Supplementation in Established High-Fat Diet-Induced Obesity Attenuates the Severity of the Obese Inflammatory Phenotype

Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HF→HFB) or LF (11% fat as kcal; HF→LF) (n = 12/group). HF→HFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmβ, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HF→LF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HF→HFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HF→HFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.     

High-Load Resistance Exercise Augments Androgen Receptor–DNA Binding and Wnt/β-Catenin Signaling without Increases in Serum/Muscle Androgens or Androgen Receptor Content

The purpose of this study was (1) to determine the effect of single bouts of volume- and intensity-equated low- (LL) and high-load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding; and, (2) to determine the effect of RE on sarcoplasmic and nucleoplasmic β-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. In a cross-over design, 10 resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3 h-, and 24 h post-exercise. Separate 2 × 3 factorial analyses of variance (ANOVAs) with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze the main effects. No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p > 0.05). Serum-free testosterone was significantly decreased 3 h post-exercise and remained significantly less than baseline 24 h post-exercise in both conditions (p < 0.05). In response to HL, AR-DNA binding significantly increased at 3 h post-exercise (p < 0.05), whereas no significant differences were observed at any time in response to LL (p > 0.05). Moreover, sarcoplasmic β-catenin was significantly greater in HL (p < 0.05) without significant changes in nucleoplasmic β-catenin (p > 0.05). In conclusion, increases in AR-DNA binding in response to HL RE indicate AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic β-catenin suggests β-catenin may be facilitating this response.