Hippocampal BDNF mediated anxiety-like behaviours induced by obesogenic diet withdrawal.

Obesogenic diets (ODs) consumption is associated with anxiety-like behaviour and negative changes in hippocampal BDNF. At the same time, interrupting OD intake, OD withdrawal (WTD), can bring health benefits, but previous studies reported the development of anxiety-like behaviours. The present work aimed to assess the relationship between anxiety-like behaviour with hippocampal BDNF in a WTD rodent model. Male Wistar rats (60d old) were fed a high-sugar/high-fat (HSHF) diet for 30d (n = 32), and half of them were transitioned to a control diet for 48 h (n = 16) afterwards. The control group (n = 16) was fed a control diet across the whole experiment. Besides increasing anxiety-like behaviours and lowering sociability, the WTD led to an increase in BDNF in the dentate gyrus and the CA1 of the hippocampus. It also decreased locomotor activity in both OF and EPM, however, they did not significantly interfere with the other behavioural parameters analysed. Western blotting analysis revealed that the increase in BDNF likely occurred in the mature forms (14 kD monomer and 28 kD dimer). The mediation models analyses suggested that the effect of WTD on anxiety-like behaviour was driven by hippocampal BDNF, this mediation of effect was region-dependent. Our results also suggested that mature BDNF forms (14 kD and 28 kD) were responsible. The present work brought light to a possible new role for mature BDNF, although it is generally associated with beneficial features, it can also be part of the genesis of anxiety-like behaviours and sociability aspects on WTD models.

IL10/AMPK pathway was associated with the hippocampal anti-inflammatory response to high-sugar and high-fat diet withdrawal.

OBJECTIVE: The present experimental study aimed to evaluate the effect of consuming an obesogenic diet (OD) on serum and hippocampal inflammation and proteins related to energy metabolism, alongside, we evaluated how the same parameters responded to an OD withdrawal. SUBJECTS: Thirty male 60-days-old Wistar rats were used. METHODS: The control group (n = 10) was fed the control diet across the whole experiment. The remaining animals were fed a high-sugar/high-fat (HSHF) diet for 30 days (n = 20) and half of them were placed on the control diet for 48 h (n = 10) afterwards. RESULTS: OD intake decreased hippocampal AMPK phosphorylation, although, it did not increase serum inflammation and only increased hippocampal pNFκBp65 levels without any increase in the cytokines assessed. Moreover, OD withdrawal led to higher inflammatory markers in the serum and hippocampus and higher hippocampal AMPK phosphorylation. The mediation models applied suggested that the effect of OD withdrawal on hippocampal inflammation was driven by serum inflammation, which activated the hippocampal IL10/AMPK anti-inflammatory pathway as a response. CONCLUSION: Our analyses suggest that OD withdrawal increases serum inflammation with hippocampal consequent inflammatory alterations. Despite the general assumption that improving diet improves health, this may not be immediate.

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.

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.

AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model.

Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. The obesity propensity is more associated with energy intake than expenditure dysregulations and may have a link with AMPK activity. While the effects of ODs are studied widely, few evaluate the short-term effects of terminating OD intake. Withdrawing from OD (WTD) is thought to improve or reverse the damages caused by the intake. Therefore, here we applied an OD intake and WTD protocol aiming to evaluate AMPK protein content and phosphorylation in the colon, liver, and hypothalamus and their relationship with obesity propensity. To this end, male Wistar rats (60 days) received control or high-sugar/high-fat (HSHF) OD for 30 days. Half of the animals were OD-withdrawn and fed the control diet for 48 h. After intake, we found a reduction in AMPK phosphorylation in the hypothalamus and colon, and after WTD, we found an increase in its hepatic and hypothalamic phosphorylation. The decrease in colon pAMPK/AMPK could be linked with hypothalamic pAMPK/AMPK after HSHF intake, while the increase in hepatic pAMPK/AMPK could have prevented the increase in hypothalamic pAMPK/AMPK. In the obesity-prone rats, we found higher levels of hypothalamic and colon pAMPK/AMPK despite the higher body mass gain. Our results highlight the relevance in multi-organ investigations and animal phenotype evaluation when studying the energy metabolism regulations.

Hepatic inflammation precedes steatosis and is mediated by visceral fat accumulation.

The negative aspects of unhealthy eating on obesity and hepatic health are well described. The axis between the adipose tissue and the liver participates in most of the damage caused to this tissue regarding obesogenic diets (OD). At the same time that the effects of consuming simple carbohydrates and saturated fatty acids are known, the effects of the cessation of its intake are scarce. Withdrawing from OD is thought to improve health; despite some studies had shown improvement in hepatic conditions in the long-term, short-term studies were not found. Therefore, we aimed to determine how OD intake and withdrawal would influence visceral and hepatic fat accumulation and inflammation. To this end, male 60-days-old Wistar rats received standard chow (n = 16) or a high-sugar/high-fat diet (HSHF) for 30 days (n = 32), a cohort of the HSHF-fed animals was then kept 48 h on standard chow (n = 16). In opposition to the generally reported, the results indicate that hepatic inflammation preceded hepatic steatosis. Additionally, inflammatory markers on the liver positively correlated visceral adipokines and visceral fat accumulation mediated them in a deposit-dependent manner. At the same time, a 48-h withdrawal was capable of reverting most of the risen inflammatory mediators, although MyD88 and TNFα persisted and serum non-HDL cholesterol was higher than control levels.

Prebiotic potencial of juçara berry on changes in gut bacteria and acetate of individuals with obesity.

PURPOSE: Whole plant foods can be fermentable by SCFA-producing bacteria and positively influence host adipose tissue development and obesity related-metabolic disorders, conferring a prebiotic role. Considering the juçara berry composition, rich in fiber and polyphenols, we hypothesized the probable prebiotic role of juçara in individuals with obesity. METHODS: It was a randomized double-blind placebo-controlled trial with 35 volunteers with obesity I and II of both sexes aged from 31 to 59 years, divided into juçara group (5 g lyophilized juçara) or placebo group (5 g of maltodextrin) for 6 weeks. Before and after supplementation, food intake and blood and stool samples were collected to evaluate serum LPS, SCFA, and microbial bacteria. RESULTS: Significant increase in fecal acetate (g = 0.809; p = 0.038) and in relative abundance of A. muciniphila, Bifidobacterium spp. and C. coccoides were observed in response to juçara supplementation (Δ% = 239.6%, 182.6%, and 214%, respectively), with a significant mediator role of Bifidobacterium spp. in high amounts of fecal acetate (z = 2.925; p = 0.003). To certify the prebiotic role of juçara, the averages were adjusted for total fiber intake; and there was no effect of the fiber intake on the SCFA nor on the intestinal bacteria. CONCLUSION: Juçara berry may haveprebiotic function, with emphasis on the bifidogenic effect, leading to increased excretion of acetate.