Nutrition

Maternal betaine protects rat offspring from glucocorticoid-induced activation of lipolytic genes in adipose tissue through modification of DNA methylation Abstract Purpose Excessive exposure of glucocorticoids activates adipose lipolysis, increases circulating free fatty acids, and contributes to ectopic lipid deposition in liver and skeletal muscle. Our previous study demonstrated that maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid accumulation in rat offspring. However, it is unclear whether maternal betaine supplementation is effective in preventing glucocorticoid-induced lipolysis in the adipose tissue of offspring. Methods In this study, 20 pregnant rats were fed with basal or betaine-supplemented (10 g/kg) diets throughout gestation and lactation, and the offspring rats were raised on the basal diet from weaning till 3 months of age followed by daily intraperitoneal injection of saline or 0.1 mg/kg dexamethasone (DEX) for 3 weeks. Results Chronic DEX treatment significantly (P < 0.05) decreased serum corticosterone level and increased proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. Meanwhile, GR protein content in adipose tissue was increased in response to DEX treatment, which was associated with a significant (P < 0.05) up-regulation of ATGL and HSL expression at both mRNA and protein levels. All these DEX-induced changes were significantly (P < 0.05) attenuated in progeny rats derived from betaine-supplemented dams. Furthermore, DEX-induced hypomethylation of ATGL and HSL gene promoters was reversed by maternal betaine supplementation. Conclusions Taken together, these results suggest that maternal betaine supplementation is effective in alleviating glucocorticoid-induced lipolysis in adipose tissue with modification of DNA methylation on the promoter of lipolytic genes.

Obesity-related inflammatory modulation by juçara berry ( Euterpe edulis Mart.) supplementation in Brazilian adults: a double-blind randomized controlled trial Abstract Purpose Obesity is an inflammatory-related disease, which recruits immune system cells triggering to imbalanced production of cytokines. Obesity management and treatment using foods bioactive compounds have gained clinical and scientific relevance. Juçara (Euterpe edulis Mart.) fruit is rich in fibers, unsaturated lipids and, anthocyanins showing potential health benefits. Thus, we investigated the effect of juçara pulp intake on inflammatory status of monocytes from obese individuals. Methods It is a placebo-controlled, randomized double-blind trial. Twenty-seven obese participants (BMI between 30.0 and 39.9 kg/m2) of both genders from 31 to 59-year-old, divided into two groups: 5 g juçara freeze-dried pulp or 5 g of placebo for 6 weeks. Before and after supplementation, blood samples were collected and monocytes obtained and stimulated with lipopolysaccharides. After 24 h of incubation, the cells and supernatants were analyzed. Results Post-treatment, juçara reduced TLR4, and IL-6 mRNA compared to placebo. Juçara also increased IL-10 mRNA in post-treatment. The protein expression of TLR4 pathway post-treatment, MYD88 expression reduced in juçara group compared to placebo. The juçara post-treatment reduced pIKKα/β compared to the placebo. Ob-R protein levels were higher in the juçara group post-treatment compared to pre-treatment. IL-6, TNF-α, and MCP-1 production by monocytes were reduced by juçara in post-treatment compared to pre-treatment levels. The supplementation increased IL-10 in juçara group with LPS compared to pre-treatment and versus juçara group without LPS. Conclusion These results demonstrated a proinflammatory state at the beginning, which was improved by juçara pulp consumption. Our results suggest juçara pulp as a potential tool against the proinflammatory status of obesity.

Effects of a formula with a probiotic Bifidobacterium lactis Supplement on the gut microbiota of low birth weight infants Abstract Purpose Low birth weight (LBW) infants have a less diverse gut microbiota, enriched in potential pathogens, which places them at high risk of systemic inflammation diseases. This study aimed to identify the differences in gut bacterial community structure between LBW infants who received probiotics and LBW infants who did not receive probiotics. Methods Forty-one infants were allocated to the non-probiotic group (N group) and 56 infants to the probiotic group (P group), according to whether the formula they received contained a probiotic Bifidobacterium lactis. Gut bacterial composition was identified with sequencing of the 16S rRNA gene in fecal samples collected at 14 days after birth. Results There was no significant difference between the alpha diversity of the two groups, while the beta diversity was significantly different (p < 0.05). Our results showed that Bifidobacterium and Lactobacillus (both p < 0.05) were enriched in the P group, while Veillonella, Dolosigranulum and Clostridium sensu stricto 1 (all p < 0.05) were enriched in the N group. Predicted metagenome function analysis revealed enhancement of fatty acids, peroxisome, starch, alanine, tyrosine and peroxisome pathways in the P group, and enhancement of plant pathogen, Salmonella and Helicobacter pylori infection pathways in the N group. Conclusions Probiotic supplement in formula may affect the composition, stability and function of LBW infants’ gut microbiota. LBW infants who receive probiotic intervention may benefit from gut microbiota that contains more beneficial bacteria.

The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women Abstract Purpose A technological gap exists for the iron (Fe) fortification of difficult-to-fortify products, such as wet and acid food products containing polyphenols, with stable and bioavailable Fe. Fe picolinate, a novel food ingredient, was found to be stable over time in this type of matrix. The objective of this study was to measure the Fe bioavailability of Fe picolinate in a complementary fruit yogurt. Methods The bioavailability of Fe picolinate was determined using stable iron isotopes in a double blind, randomized cross-over design in non-anemic Swiss women (n = 19; 25.1 ± 4.6 years). Fractional Fe absorption was measured from Fe picolinate (2.5 mg 57Fe per serving in two servings given morning and afternoon) and from Fe sulfate (2.5 mg 54Fe per serving in two servings given morning and afternoon) in a fortified dairy complementary food (i.e. yogurt containing fruits). Fe absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. Results Geometric mean (95% CI) fractional iron absorption from Fe picolinate and Fe sulfate were not significantly different: 5.2% (3.8–7.2%) and 5.3% (3.8–7.3%) (N.S.), respectively. Relative bioavailability of Fe picolinate versus Fe sulfate was 0.99 (0.85–1.15). Conclusion Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.

l -Theanine promotes cultured human Sertoli cells proliferation and modulates glucose metabolism Abstract Purpose l-Theanine is the major free amino acid present in tea (Camellia sinensis L.). The effects of several tea constituents on male reproduction have been investigated, but l-theanine has been overlooked. Sertoli cells (SCs) are essential for the physical and nutritional support of germ cells. In this study, we aimed to investigate the ability of l-theanine to modulate important mechanisms of human SCs (hSCs) metabolism, mitochondrial function and oxidative profile, which are essential to prevent or counteract spermatogenesis disruption in several health conditions. Methods We evaluated the effect of a dose of l-theanine attained by tea intake (5 μM) or a pharmacological dose (50 μM) on the metabolism (proton nuclear magnetic resonance and Western blot), mitochondrial functionality (protein expression of mitochondrial complexes and JC1 ratio) and oxidative profile (carbonyl levels, nitration and lipid peroxidation) of cultured hSCs. Results Exposure of hSCs to 50 µM of l-theanine increased cell proliferation and glucose consumption. In response to this metabolic adaptation, there was an increase in mitochondrial membrane potential, which may compromise the prooxidant–antioxidant balance. Still, no alterations were observed regarding the oxidative damages. Conclusions A pharmacological dose of l-theanine (50 µM) prompts an increase in hSCs proliferation and a higher glucose metabolization to sustain the pool of Krebs cycle intermediates, which are crucial for cellular bioenergetics and biosynthesis. This study suggests an interplay between glycolysis and glutaminolysis in the regulation of hSCs metabolism.

Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner Abstract Purpose Pomegranate and walnuts are widely consumed dietary sources and contain several bioactive compounds, including the ellagitannins (ETs). ETs are polyphenols that are metabolized in the gut microbiota to urolithin A (UA). p53 is a tumor suppressor that lost its activity through MDM2 activation in about half cancers. The purpose of this study was to investigate the influence of UA on the p53-MDM2 interaction pathway in prostate cancer cell lines. Methods Three human prostate cancer cell lines were used that harbor different p53 genotypes; LNCaP (p53+/+), 22RV1(p53−/+) and PC3 (p53−/−). Cell viability was determined by CellTiter-Glo Luminescent assay. Apoptosis was confirmed by measuring annexin V by flow cytometry. The expression of p53, its target proteins, and apoptotic markers were measured by western blotting. Real-time qPCR was used to measure the gene expression of p21, a main target gene of p53. Co-immunoprecipitation–immunoblotting was used to assess the inhibition of interactions between p53 and MDM2 and to assess the effect of UA on MDM2-mediated p53 polyubiquitination. Results We found UA inhibited CaP cells’ viability and induced apoptosis. For 22RV1 and LNCaP, we found UA increased p53 protein expression and its main target protein, p21, and MDM2, forming an autoregulatory feedback loop. In addition, UA increased the p53 proapoptotic proteins PUMA and NOXA. Moreover, UA inhibited the interaction between p53 and MDM2 and inhibited MDM2-mediated p53 polyubiquitination. UA downregulated MDM2 and XIAP protein expression in PC3 cells and upregulated p21 and p14ARF in a p53-independent manner. Conclusion The influencing of UA on p53-MDM2 pathway may partly contribute to its anticancer effect.

Association between fruit and vegetable consumption and risk of metabolic syndrome determined using the Korean Genome and Epidemiology Study (KoGES) Abstract Purpose This study examined the association between fruit and vegetable consumption and the risk of metabolic syndrome (MetS) and its components in middle-aged and older adults using data from the Korean Genome and Epidemiology Study. Methods A total of 5688 participants aged 40–69 years without MetS at baseline were recruited and followed for 8 years. Fruit and vegetable consumption was assessed using a semi-quantitative food-frequency questionnaire at baseline and after 4 years. A multivariate Cox proportional hazards model was used to examine the risk of incident MetS and its components according to fruit and vegetable consumption. Results A total of 2067 participants (1020 men and 1047 women) developed MetS during the 8-year follow-up period. Frequent fruit consumers (≥ 4 servings/day) had a lower risk of incident MetS than did rare consumers (< 1 serving/day) in both men and women (hazard ratio (HR) = 0.55, 95% CI 0.44–0.67, p < 0.0001 for men; HR = 0.57, 95% CI 0.47–0.70, p for trend < 0.0001 for women) after adjusting for confounders. Frequent fruit consumption was inversely associated with incidence of abdominal obesity, hypertriglyceridemia, and elevated blood pressure. Frequent vegetable consumption was inversely associated with a risk of hyperglycemia only in men (HR = 0.65, 95% CI 0.44–0.96, p for trend = 0.0275), but no association was observed with risk of incident MetS. Conclusions High fruit consumption was associated with a reduced risk of incident MetS and its components, whereas high vegetable consumption was associated with a reduced risk of incident hyperglycemia, but not with MetS in middle-aged and older adults.

Intakes of long-chain omega-3 polyunsaturated fatty acids and non-fried fish in relation to incidence of chronic kidney disease in young adults: a 25-year follow-up Abstract Purpose The prevalence of chronic kidney disease (CKD) is increasing rapidly in many countries and has become a major public health concern. Although intakes of long-chain omega-3 polyunsaturated fatty acids (LCω3PUFA) and its food source—fish—may have renal protective effects, little is known about the longitudinal association between these dietary factors and CKD incidence. Methods A total of 4133 healthy individuals of black and white race aged 18–30 at baseline (1985–1986) from the Coronary Artery Risk Development in Young Adults study were enrolled and followed up over 25 years. LCω3PUFA and fish intake were assessed by an interview-based dietary history questionnaire at baseline, year 7 (1992–1993) and 20 (2005–2006). Results Four hundred and eighty-nine incident cases of CKD were identified. After adjustment for potential confounders, LCω3PUFA intake was inversely associated with CKD incidence [HR = 0.73 (95% CI 0.60–0.89), P = 0.002, with one standard division (0.19 g/day) increment in LCω3PUFA]. This inverse association was persisted among females [0.64 (95% CI 0.48, 0.84; P = 0.002], but not males (Pinteraction = 0.070). A marginal significant inverse association was also found between non-fried fish consumption and CKD incidence (HR = 0.86, 95% CI 0.73, 1.01; P = 0.073). Conclusions Dietary LCω3PUFA intake was inversely associated with incidence of CKD among American young adults over 25 years of follow-up. The suggestive evidence of the inverse association between non-fried fish consumption with CKD incidence needs further confirmation.

High-fat diet induced central adiposity (visceral fat) is associated with increased fibrosis and decreased immune cellularity of the mesenteric lymph node in mice Abstract Purpose Accumulation of visceral, but not subcutaneous, adipose tissue is highly associated with metabolic disease. Inflammation inciting from adipose tissue is commonly associated with metabolic disease risk and comorbidities. However, constituents of the immune system, lymph nodes, embedded within these adipose depots remain under-investigated. We hypothesize that, lymph nodes are inherently distinct and differentially respond to diet-induced obesity much like the adipose depots they reside in. Methods Adipose tissue and lymph nodes were collected from the visceral and inguinal depots of male mice fed 13 weeks of standard CHOW or high fat diet (HFD). Immune cells were isolated from tissues, counted and characterized by flow cytometry or plated for proliferative capacity following Concanavalin A stimulation. Lymph node size and fibrosis area were also characterized. Results In HFD fed mice visceral adipose tissue accumulation was associated with significant enlargement of the lymph node encased within. The subcutaneous lymph node did not change. Compared with mice fed CHOW for 13 weeks, mice fed HFD had a decline in immune cell populations and immune cell proliferative ability, as well as, exacerbated fibrosis accumulation, within the visceral, but not subcutaneous, lymph node. Conclusions Obesity-induced chronic low-grade inflammation is associated with impaired immunity and increased susceptibility to disease. Excessive visceral adiposity and associated inflammation driven by diet likely leads to obesity-induced immune suppression by way of lymph node/lymphatic system pathophysiology.

Moderate chronic ethanol consumption exerts beneficial effects on nonalcoholic fatty liver in mice fed a high-fat diet: possible role of higher formation of triglycerides enriched in monounsaturated fatty acids Abstract Purpose Several clinical studies suggested that light-to-moderate alcohol intake could alleviate nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism is still poorly understood. Methods Mice fed a high-fat diet (HFD) were submitted or not to moderate ethanol intake for 3 months (ca. 10 g/kg/day) via drinking water. Biochemical, analytical and transcriptomic analyses were performed in serum and liver. Results Serum ethanol concentrations in ethanol-treated HFD mice comprised between 0.5 and 0.7 g/l throughout the experiment. NAFLD improvement was observed in ethanol-treated HFD mice as assessed by reduced serum transaminase activity. This was associated with less microvesicular and more macrovacuolar steatosis, the absence of apoptotic hepatocytes and a trend towards less fibrosis. Liver lipid analysis showed increased amounts of fatty acids incorporated in triglycerides and phospholipids, reduced proportion of palmitic acid in total lipids and higher desaturation index, thus suggesting enhanced stearoyl-coenzyme A desaturase activity. mRNA expression of several glycolytic and lipogenic enzymes was upregulated. Genome-wide expression profiling and gene set enrichment analysis revealed an overall downregulation of the expression of genes involved in collagen fibril organization and leukocyte chemotaxis and an overall upregulation of the expression of genes involved in oxidative phosphorylation and mitochondrial respiratory chain complex assembly. In addition, mRNA expression of several proteasome subunits was upregulated in ethanol-treated HFD mice. Conclusions Moderate chronic ethanol consumption may alleviate NAFLD by several mechanisms including the generation of non-toxic lipid species, reduced expression of profibrotic and proinflammatory genes, restoration of mitochondrial function and possible stimulation of proteasome activity.