Parental high-fat high-sugar diet programming and hypothalamus adipose tissue axis in male Wistar rats.

PURPOSE: Maternal nutrition during early development and paternal nutrition pre-conception can programme offspring health status. Hypothalamus adipose axis is a target of developmental programming, and paternal and maternal high-fat, high-sugar diet (HFS) may be an important factor that predisposes offspring to develop obesity later in life. This study aims to investigate Wistar rats' maternal and paternal HFS differential contribution on the development, adiposity, and hypothalamic inflammation in male offspring from weaning until adulthood. METHODS: Male progenitors were fed a control diet (CD) or HFS for 10 weeks before mating. After mating, dams were fed CD or HFS only during pregnancy and lactation. Forming the following male offspring groups: CD-maternal and paternal CD; MH-maternal HFS and paternal CD; PH-maternal CD and paternal HFS; PMH-maternal and paternal HFS. After weaning, male offspring were fed CD until adulthood. RESULTS: Maternal HFS diet increased weight, visceral adiposity, and serum total cholesterol levels, and decreased hypothalamic weight in weanling male rats. In adult male offspring, maternal HFS increased weight, glucose levels, and hypothalamic NFκBp65. Paternal HFS diet lowered hypothalamic insulin receptor levels in weanling offspring and glucose and insulin levels in adult offspring. The combined effects of maternal and paternal HFS diets increased triacylglycerol, leptin levels, and hypothalamic inflammation in weanling rats, and increased visceral adiposity in adulthood. CONCLUSION: Male offspring intake of CD diet after weaning reversed part of the effects of parental HFS diet during the perinatal period. However, maternal and paternal HFS diet affected adiposity and hypothalamic inflammation, which remained until adulthood.

Obesity-related inflammatory modulation by juçara berry (Euterpe edulis Mart.) supplementation in Brazilian adults: a double-blind randomized controlled trial.

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/ß 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.

Programming mediated by fatty acids affects uncoupling protein 1 (UCP-1) in brown adipose tissue.

Brown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.

The Use of Juçara (Euterpe edulis Mart.) Supplementation for Suppression of NF-κB Pathway in the Hypothalamus after High-Fat Diet in Wistar Rats.

Obesity is associated with modern diets that are rich in saturated fatty acids. These dietary patterns are linked to low-grade proinflammatory mechanisms, such as the toll-like receptor 4/nuclear factor kappa-B (NF-κB) pathway rapidly activated through high-fat diets. Juçara is a berry rich in anthocyanins and unsaturated fatty acids, which prevents obesity and associated comorbidities. We evaluated the effect of different doses of freeze-dried juçara pulp on NF-κB pathway after the consumption of short-term high-fat diet. Male Wistar rats with ad libitum access to food and water were divided into four groups: Control diet (C), high-fat diet (HFC), high-fat diet with 0.25% juçara (HFJ 0.25%), and high-fat diet with 0.5% juçara (HFJ 0.5%). Energy intake and body weight gain were increased in HFC and HFJ 0.5% groups compared to C group. The hypothalamus weight reduced in the HFC group compared to C and HFJ 0.25% groups. Cytokines, MYD88, TRAF6, and pNF-κBp50 levels in the hypothalamus, serum triacylglycerol, LDL-cholesterol (LDL-C), and free fatty acid levels were improved in the HFJ 0.25% group. In summary, the HFJ 0.25% group had better protective effects than those in the HFJ 0.5%. Therefore, 0.25% juçara can be used to protect against central inflammation through the high-fat diet-induced NF-κB pathway.

Leptin as a cardiovascular risk marker in metabolically healthy obese: Hyperleptinemia in metabolically healthy obese.

Adipokines contribute to the inflammatory process which can lead to obesity-associated cardiometabolic complications. Metabolically healthy obese individuals seem to be protected or more resistant to develop these complications and it is intriguing why some individuals develop comorbidities and others do not. Thus, we questioned whether the differences between metabolically healthy and unhealthy obese relied on the alterations in metabolic profile, characterized by serum leptin and adiponectin. A total of 142 obese adults were divided into 2 groups - metabolically healthy obese (MHO) or unhealthy obese (MUO) - and they were evaluated for anthropometric measures, body composition, blood pressure, dietary intakes and plasma levels of leptin and adiponectin. Leptin/adiponectin ratio (L/A) was calculated. Age, BMI and blood pressure were higher in the MUO. No differences in anthropometric measurements, body composition, dietary intake and dietary quality were observed between groups. Leptin were significantly higher in the MUO (53.07 ± 34.56 versus 36.27 ± 24.02 ng/ml in the MHO, r < 0.04). The logistic regression analysis demonstrated that leptin was an important factor associated with not being healthy, independent of age, body weight and BMI. There were no differences between groups for adiponectin and L/A. Leptin correlated positively with body weight (r = 0.25, r < 0.05), BMI (r = 0.38, r < 0.05) and BF (r = 0.74, r < 0.05), and negatively with FFM (r = -0.74, r < 0.05). Our findings suggest that leptin is an important cardiovascular disease marker to obese population and can contribute to evaluate metabolic risks in these individuals.

Parental High-Fat High-Sugar Diet Intake Programming Inflammatory and Oxidative Parameters of Reproductive Health in Male Offspring.

Parental nutrition can impact the health of future generations, programming the offspring for the development of diseases. The developing germ cells of the offspring could be damaged by the maternal or the paternal environment. The germ cells in development and their function could be affected by nutritional adversity and therefore, harm the health of subsequent generations. The paternal or maternal intake of high-fat diets has been shown to affect the reproductive health of male offspring, leading to imbalance in hypothalamic-pituitary-gonadal axis, testicular oxidative stress, low testosterone production, and changes in sperm count, viability, motility, and morphology. There is a need for studies that address the combined effects of diets with a high-fat and high-sugar (H) content by both progenitors on male reproduction. In this context, our study evaluated epigenetic parameters and the inflammatory response that could be associated to oxidative stress in testis and epididymis of adult offspring. 90 days-old male rats were divided according to the combination of the parental diet: CD (control paternal and maternal diet), HP (H paternal diet and control maternal diet), HM (H maternal diet and control paternal diet) and HPM (H paternal and maternal diet).We evaluated serum levels of testosterone and FSH; testicular gene expression of steroidogenic enzymes Star and Hsd17b3 and epigenetic markers Dnmt1, Dnmt3a, Dnmt3b, and Mecp2; testicular and epididymal levels of TNF-α, IL-6, IL-10, and IL-1ß; testicular and epididymal activity of SOD, CAT, and GST; the oxidative markers MDA and CP; the daily sperm production, sperm transit time, and sperm morphology. Testicular epigenetic parameter, inflammatory response, oxidative balance, and daily sperm production of the offspring were affected by the maternal diet; paternal diet influenced serum testosterone levels, and lower daily sperm production was exacerbated by the interaction effect of both parental intake of high-fat high-sugar diet in the testis. There was isolated maternal and paternal effect in the antioxidant enzyme activity in the cauda epididymis, and an interaction effect of both parents in protein oxidative marker. Maternal effect could also be observed in cytokine production of cauda epididymis, and no morphological effects were observed in the sperm. The potential programming effects of isolated or combined intake of a high-fat high-sugar diet by the progenitors could be observed at a molecular level in the reproductive health of male offspring in early adulthood.

The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring.

PURPOSE: The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood. METHODS: For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; FaecalBifidobacterium spp.andLactobacillus spp. DNA. RESULTS: Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecalBifidobacteriumspp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecalBifidobacteriumspp. andLactobacillusspp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lowerBifidobacteriumspp. andLactobacillus spp.in the adult offspring. CONCLUSION: Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood.

Supplementation of Juçara Berry (Euterpe edulis Mart.) Modulates Epigenetic Markers in Monocytes from Obese Adults: A Double-Blind Randomized Trial.

Nutrigenomics is an emerging field in obesity since epigenetic markers can be modified by environmental factors including diet. Considering juçara composition-rich in anthocyanins, monounsaturated fatty acids (MUFAs) and fibers-it has the potential for epigenetic modulation. We evaluated the juçara supplementation modulating the serum fatty acids profile and epigenetic markers in monocytes of adult obese humans. It was a randomized double-blind, controlled trial with 27 obese (Body mass index between 30.0 and 39.9 kg/m²) participants of both genders aged from 31 to 59 years, divided into juçara group (5 g juçara freeze-dried pulp) or placebo group (5 g of maltodextrin) for 6 weeks. Before and after supplementation, blood samples were collected. The serum and monocytes cells obtained were cultured and stimulated with lipopolysaccharides as proinflammatory stimulus. After 24 h of incubation, the cells and supernatants were collected and analyzed. Juçara improved the serum fatty acids profile on unsaturated fatty acids levels. The epigenetic markers evaluated were improved post-treatment. Also, the methylated DNA level was increased after treatment. We find that juçara supplementation is a predictor of methyl CpG binding proteins 2 (MeCP2) in monocytes. Concluding, juçara supplementation improved the serum fatty acids profile, modulating the epigenetic markers in monocytes from obese individuals.

Fatty-acid-mediated hypothalamic inflammation and epigenetic programming.

A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity. We found few experimental studies that looked at programming induced by different fatty acids on the hypothalamus. They clearly showed a connection between maternal fat diet, hypothalamic inflammation and metabolic alterations in the offspring. We found that not only a high-fat diet but also a normolipidic diet with unbalanced quantities of different fatty acids produced diverse inflammatory responses on the hypothalamus. Therefore, strategies of manipulating dietary fatty acids in pregnant and lactating women may have great impact on the population's future health. However, more research is still needed on the effects of fatty acids and the hypothalamic inflammation on programming.