Effect of modified citrus pectin on galectin-3 inhibition in cisplatin-induced cardiac and renal toxicity.

This study evaluated the effect of pharmacological inhibition of galectin 3 (Gal-3) with modified citrus pectin (MCP) on the heart and kidney in a model of cisplatin-induced acute toxicity. Male Wistar rats were divided into four groups (n = 6/group): SHAM, which received sterile saline intraperitoneally (i.p.) for three days; CIS, which received cisplatin i.p. (10 mg/kg/day) for three days; MCP, which received MCP orally (100 mg/kg/day) for seven days, followed by sterile saline i.p. for three days; MCP+CIS, which received MCP orally for seven days followed by cisplatin i.p. for three days. The blood, heart, and kidneys were collected six hours after the last treatment. MCP treatment did not change Gal-3 protein levels in the blood and heart, but it did reduce them in the kidneys of the MCP groups compared to the SHAM group. While no morphological changes were evident in the cardiac tissue, increased malondialdehyde (MDA) levels and deregulation of the mitochondrial oxidative phosphorylation system were observed in the heart homogenates of the MCP+CIS group. Cisplatin administration caused acute tubular degeneration in the kidneys; the MCP+CIS group also showed increased MDA levels. In conclusion, MCP therapy in the acute model of cisplatin-induced toxicity increases oxidative stress in cardiac and renal tissues. Further investigations are needed to determine the beneficial and harmful roles of Gal-3 in the cardiorenal system since it can act differently in acute and chronic diseases/conditions.

Kinin B1 receptor controls maternal adiponectin levels and influences offspring weight gain.

Given the importance of the kinin B1 receptor in insulin and leptin hormonal regulation, which in turn is crucial in maternal adaptations to ensure nutrient supply to the fetus, we investigated the role of this receptor in maternal metabolism and fetoplacental development. Wild-type and kinin B1 receptor-deficient (B1KO) female mice were mated with male mice of the opposite genotype. Consequently, the entire litter was heterozygous for kinin B1 receptor, ensuring that there would be no influence of offspring genotype on the maternal phenotype. Maternal kinin B1 receptor blockade reduces adiponectin secretion by adipose tissue ex vivo, consistent with lower adiponectin levels in pregnant B1KO mice. Furthermore, fasting insulinemia also increased, which was associated with placental insulin resistance, reduced placental glycogen accumulation, and heavier offspring. Therefore, we propose the combination of chronic hyperinsulinemia and reduced adiponectin secretion in B1KO female mice create a maternal obesogenic environment that results in heavier pups.

An interdisciplinary therapy for lifestyle change is effective in improving psychological and inflammatory parameters in women with grade I obesity.

Obesity and depression, disorders associated with inflammation, have high incidences in women. Understanding the derangements present in the initial phase of obesity may point to factors that could help avoiding disease aggravation. The present study aimed at investigating the effects of a 6-months interdisciplinary therapy for weight loss in women with grade I obesity. Before and after the therapy, 37 middle-aged women donated blood and responded to questionnaires for depression and anxiety symptoms. Inflammatory parameters were evaluated in serum and a preliminary screening of the plasma proteome was performed. The therapy decreased anthropometric, psychological scores, and serum levels of inflammatory parameters. Depression and anxiety scores correlated positively with some inflammatory parameters. The proteomic analysis showed changes in proteins related to cholesterol metabolism and inflammatory response. Interdisciplinary therapy improves anthropometric and inflammatory statuses and ameliorating psychological symptoms. The decrease of MCP-1 levels after interdisciplinary therapy has not been reported so far, at the best of our knowledge. The present demonstration of positive associations of inflammatory markers and psychological scores indicate that these mediators may be useful to monitor psychological status in obesity. The present proteome data, although preliminary, pointed to plasma alterations indicative of improvement of inflammation after interdisciplinary therapy.

Plasma signatures of Congenital Generalized Lipodystrophy patients identified by untargeted lipidomic profiling are not changed after a fat-containing breakfast meal.

BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal. METHOD: Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry. RESULTS: Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants. CONCLUSIONS: The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.

Severe Obesity in Women Can Lead to Worse Memory Function and Iron Dyshomeostasis Compared to Lower Grade Obesity.

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

Unveiling the Angiotensin-(1-7) Actions on the Urinary Bladder in Female Rats.

Angiotensin-(1-7) is a peptide produced by different pathways, and regardless of the route, the angiotensin-converting enzyme 2 (ACE-2) is involved in one of the steps of its synthesis. Angiotensin-(1-7) binds to Mas receptors localized in different cells throughout the body. Whether angiotensin-(1-7) exerts any action in the urinary bladder (UB) is still unknown. We investigated the effects of intravenous and topical (in situ) administration of angiotensin-(1-7) on intravesical pressure (IP) and cardiovascular variables. In addition, the Mas receptors and ACE-2 gene and protein expression were analyzed in the UB. Adult female Wistar rats were anesthetized with 2% isoflurane in 100% O2 and submitted to the catheterization of the femoral artery and vein for mean arterial pressure (MAP) and heart rate (HR) recordings, and infusion of drugs, respectively. The renal blood flow was acquired using a Doppler flow probe placed around the left renal artery and the renal conductance (RC) was calculated as a ratio of Doppler shift (kHz) and MAP. The cannulation of the UB was performed for IP recording. We observed that angiotensin-(1-7) either administered intravenously [115.8 ± 28.6% angiotensin-(1-7) vs. -2.9 ± 1.3% saline] or topically [147.4 ± 18.9% angiotensin-(1-7) vs. 3.2 ± 2.8% saline] onto the UB evoked a significant (p < 0.05) increase in IP compared to saline and yielded no changes in MAP, HR, and RC. The marked response of angiotensin-(1-7) on the UB was also investigated using quantitative real-time polymerase chain reaction and western blotting assay, which demonstrated the mRNA and protein expression of Mas receptors in the bladder, respectively. ACE-2 mRNA and protein expression was also observed in the bladder. Therefore, the findings demonstrate that angiotensin-(1-7) acts in the UB to increase the IP and suggest that this peptide can be also locally synthesized in the UB.

Retroperitoneal adipose tissue denervation improves cardiometabolic and autonomic dysfunction in a high fat diet model.

Sympathetic vasomotor overactivity is a major feature leading to the cardiovascular dysfunction related to obesity. Considering that the retroperitoneal white adipose tissue (rWAT) is an important fat visceral depot and receives intense sympathetic and afferent innervations, the present study aimed to evaluate the effects evoked by bilateral rWAT denervation in obese rats. Male Wistar rats were fed with HFD for 8 consecutive weeks and rWAT denervation was performed at the 6th week. Arterial pressure, splanchnic and renal sympathetic vasomotor nerve activities were assessed and inflammation and the components of the renin -angiotensin system were evaluated in different white adipose tissue depots. HFD animals presented higher serum levels of leptin and glucose, an increase in arterial pressure and splanchnic sympathetic nerve activity; rWAT denervation, normalized these parameters. Pro-inflammatory cytokines levels were significantly increased, as well as RAAS gene expression in WAT of HFD animals; rWAT denervation significantly attenuated these changes. In conclusion, HFD promotes vasomotor sympathetic overactivation and inflammation with repercussions on the cardiovascular system. In conclusion, the neural communication between WAT and the brain is fundamental to trigger sympathetic vasomotor activation and this pathway is a possible new therapeutic target to treat obesity-associated cardiovascular dysfunction.

Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy.

BACKGROUND: Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects. METHODS: Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination. RESULTS: The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals. CONCLUSION: The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation.

High-fat but not normal-fat intake of extra virgin olive oil modulates the liver proteome of mice.

PURPOSE: The metabolic benefits of the Mediterranean diet have been largely attributed to its olive oil content. Whether the ingested fat amount is relevant to these effects is not clear. We thus compared the effects of high-fat and normal-fat intake of extra-virgin olive oil (EVOO) on the liver proteome. METHODS: Three groups of mice were fed for 12 weeks with either normal-fat diets containing either soybean oil (control, C) or EVOO (NO) or a high-fat EVOO diet (HO). Body weight and food intake were measured weekly and serum parameters were analyzed. The liver was processed for data-independent acquisition mass spectrometry-based proteomics. The differentially expressed proteins among the groups were submitted to pathway enrichment analysis. RESULTS: The consumption of HO diet reduced food intake and serum triglycerides, while it preserved body weight gain, adiposity, and glycemia. However, it increased serum cholesterol and liver mass. The proteomic analysis showed 98 altered proteins, which were allocated in 27 significantly enriched pathways. The pathway analysis suggested stimulation of mitochondrial and peroxissomal ß-oxidation, and inhibition of lipid synthesis and gluconeogenesis in the HO group. Although the NO group failed to show significant liver proteome alterations, it presented reduced body fat, body weight gain, and serum triglycerides and glucose levels. CONCLUSION: The data indicate that the intake of the HO diet induced hepatic adjustments, which were partially successful in counteracting the detrimental outcomes of a high-fat feeding. Contrastingly, the NO diet had beneficial effects which were not accompanied by significant modifications on hepatic proteome.

Ovariectomy modifies lipid metabolism of retroperitoneal white fat in rats: a proteomic approach.

Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acid profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen 3-mo-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 mo. A subgroup of ovariectomized rats received estradiol replacement. RAT samples were analyzed with data-independent acquisitions LC-MS/MS, and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that five pathways were significantly affected by ovariectomy, namely, metabolism of lipids (including fatty acid metabolism and mitochondrial fatty acid ß-oxidation), fatty acyl-CoA biosynthesis, innate immune system (including neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (including ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acid content. The analysis of the data indicated that ovariectomy favored lipogenesis whereas it impaired fatty acid oxidation and induced a proinflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause.

Thirty-two weeks of randomized interdisciplinary therapy or combined physical training promote similar improvements in anthropometric and biochemical parameters of obese women.

BACKGROUND: Obesity is a multicausal illness that generates large expenses to health systems and also for the families of obese individuals. It is important to note that obesity disrupts all systems, generating metabolic consequences that may be irreversible. Interdisciplinary therapy is recommended as the primary method for treating obesity. However, the cost of interdisciplinary treatment can be high due to the need for various professionals, from different areas of expertise. This study compares the effects of 32 weeks of physical training combined with interdisciplinary therapy on anthropometric and biochemical parameters in obese women. METHODS: Seventy-six subjects were randomized into two groups: Group Physical Exercise (EXE) and Group Interdisciplinary Treatment (INTER), being evaluated in the initial moment and after 32 weeks. 30 subjects completed the intervention and were evaluated (EXE: N.=13; INTER: N.=17). RESULTS: Psychobiological and biochemical variables were measured. EXE and INTER were similar before treatment and both showed significantly improvements in anthropometric and biochemical parameters after interventions, without difference between groups. CONCLUSIONS: The results confirmed the relevant role of physical training or the interdisciplinary therapy on metabolic profile of obese women. We realized that physical training can be incorporated into public or private health systems as an alternative strategy for obesity control, especially in locations that do not have the possibility of offering a complete interdisciplinary therapy.

Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension.

BACKGROUND: Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges. METHOD: In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy. RESULTS: Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (∼15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats. CONCLUSION: The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.

Effect of moderate exercise under hypoxia on Th1/Th2 cytokine balance.

INTRODUCTION AND OBJECTIVE: Moderate exercise performed in normoxia can be immunostimulatory, while strenuous exercise can be immunosuppressive. However, less is known about the effects of exercise under hypoxia on cytokines. The aim of this study was to evaluate the effects of an acute exercise session performed under hypoxia similar to an altitude of 4200 m on cytokine balance. Our hypothesis was that exercise, even of moderate intensity, associated with hypoxia may induce different changes in relation to the normoxic condition. METHODS: Eight healthy male volunteers were exercised on a treadmill for 1 hour at an intensity of 50% VO2peak under normoxic or hypoxic condition (4200 m). Blood samples were collected at rest and immediately 1 hour after the exercise, respectively to determine cytokines, hormones and metabolites. The two-way ANOVA and the Bonferroni post hoc test were used and the significance adopted was P < .05. RESULTS: While IL-2, the IL-2/IL-4 ratio and glutamine decreased under hypoxia, IL-6 and IL-1ra increased. There were increases in the IL-2/IL-4 ratio, IL-6, IL-1ra and IL-10/TNF-α in normoxia. There were no differences in cortisol or glucose. CONCLUSION: Moderate exercise under hypoxia condition changes the Th1/Th2 balance including IL-2, IL-4 and TNF-α cytokines, suggesting a Th2 response after 1 hour rest.

Ginkgo biloba Extract Modulates the Retroperitoneal Fat Depot Proteome and Reduces Oxidative Stress in Diet-Induced Obese Rats.

The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy. Ginkgo biloba extract (GbE) has been described as a promising new pharmacological approach to treat obesity. In order to better comprehend the mechanisms involved with this potential effect, the present study evaluated the effects of GbE treatment on diet-induced obese rats, focusing on the proteome and the oxidative stress defense system of visceral adipose tissue. After 14 days treatment, GbE significantly modulated 25 proteins. Retroperitoneal adipose tissue of treated animals exhibited higher amounts of proteins associated with adipogenesis (decorin), carbon metabolism and mitochondrial function (citrate synthase), and a concomitant reduction in adipocyte hypertrophy. In parallel, GbE down-regulated proteins involved in oxidative stress (peroxiredoxin) and the inflammatory response (complement C3, mast cell protease 1, and Ig gamma-2B chain C region). Moreover, also related to oxidative stress defense, GbE stimulated catalase activity, reduced malondialdehyde levels (lipid peroxidation indicator), and increased lactoylglutathione lyase levels. It was concluded that GbE acts as an antioxidant agent, and improved the proteome profile and oxidative stress response in the adipose tissue of diet-induced obese rats.

High-fat diet intake induces depressive-like behavior in ovariectomized rats.

This study tested the effects of ovariectomy, allied or not to high-fat feeding and estradiol replacement, on hormonal, metabolic and behavioral parameters, to explore the connection of obesity and depression after menopause. Wistar rats were either ovariectomized or sham-operated and fed with either standard chow or lard-enriched diet for twelve weeks. Sub-groups of ovariectomized rats received estradiol replacement. Depressive-like behaviors were assessed by the forced swim test and locomotor activity was assessed by the elevated plus maze test. Ovariectomy alone increased body weight gain and feed efficiency and induced hyperleptinemia and glucose intolerance while it increased caloric intake and body adiposity only marginally. High-fat intake alone induced obesity and, in combination with ovariectomy, accentuated the ovariectomy-induced alterations. Estradiol replacement attenuated the hormonal alterations only in chow-fed rats. Ovariectomy combined with high-fat intake induced depressive-like behaviors, which were marginally attenuated by estradiol. Depressive-like behaviors were associated with metabolic and body composition parameters and with estrogen status. The data indicate that the vulnerability to develop depression after menopause is influenced by high-fat intake. It is suggested that weight management is a crucial issue in postmenopausal women, probably having a beneficial role in preventing the appearance of mental health problems.

A diet including xanthan gum triggers a pro-inflammatory response in Wistar rats inoculated with Walker 256 cells.

OBJECTIVE: The aim of this study was to evaluate the effect of adding xanthan gum to the diet of rats on the production of cytokines and pro-inflammatory factors and on tumor development in rats inoculated with Walker 256 tumor cells. METHODS: Fifty-six rats were divided into 4 groups: control diet (C), control diet with tumor (TC), xanthan gum diet (XG), xanthan gum diet with tumor (TXG). RESULTS: The ingestion of xanthan gum promotes changes in cytokine content: increasing IL-6 TNF-α and IL-10 in retroperitoneal adipose tissue compared to the control group; and increasing TNF-α in the mesenteric adipose tissue compared to the C and TXG groups. On the contrary, the addition of xanthan gum to the diet did not affect the development of Walker 256 tumors in rats. CONCLUSION: The continuous use of xanthan gum triggered a pro-inflammatory response, promoting an increase in pro-inflammatory cytokines in the adipose tissue, but it did not have an effect on the tumor development in the animals inoculated with Walker 256 tumor cells.

A proteomics-metabolomics approach indicates changes in hypothalamic glutamate-GABA metabolism of adult female rats submitted to intrauterine growth restriction.

PURPOSE: Intrauterine growth restriction (IUGR) has been shown to induce the programming of metabolic disturbances and obesity, associated with hypothalamic derangements. The present study aimed at investigating the effects of IUGR on the protein and metabolite profiles of the hypothalamus of adult female rats. METHODS: Wistar rats were mated and either had ad libitum access to food (control group) or received only 50% of the control intake (restricted group) during the whole pregnancy. Both groups ate ad libitum throughout lactation. At 4 months of age, the control and restricted female offspring was euthanized for blood and tissues collection. The hypothalami were processed for data independent acquisition mass spectrometry-based proteomics or targeted mass spectrometry-based metabolomics. RESULTS: The adult females submitted to IUGR showed increased glycemia and body adiposity, with normal body weight and food intake. IUGR modulated significantly 28 hypothalamic proteins and 7 hypothalamic metabolites. The effects of IUGR on hypothalamic proteins and metabolites included downregulation of glutamine synthetase, glutamate decarboxylase, glutamate dehydrogenase, isocitrate dehydrogenase, α-ketoglutarate, and up-regulation of NADH dehydrogenase and phosphoenolpyruvate. Integrated pathway analysis indicated that IUGR affected GABAergic synapse, glutamate metabolism, and TCA cycle, highly interconnected pathways whose derangement has potentially multiple consequences. CONCLUSION: The present findings suggested that the effects of IUGR on GABA/glutamate-glutamine cycle may be involved in the programming of obesity and hyperglycemia in female rats.

Corrigendum: High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats.

[This corrects the article DOI: 10.3389/fnins.2018.00557.].

High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats.

Menopause-induced changes may include increased incidence of both depression/anxiety and obesity. We hypothesized that behavioral changes that may develop after ovarian failure could be related to neurochemical and metabolic aspects affected by this condition and that high-fat intake may influence these associations. The present study investigated in rats the effects of ovariectomy, either alone or combined with high-fat diets enriched with either lard or fish-oil, on metabolic, behavioral and monoaminergic statuses, and on gene expression of neuropeptides and receptors involved in energy balance and mood regulation. Female rats had their ovaries removed and received either standard chow (OvxC) or high-fat diets enriched with either lard (OvxL) or fish-oil (OvxF) for 8 weeks. The Sham group received only chow diet. Ovariectomy increased feed efficiency and body weight gain and impaired glucose homeostasis and serotonin-induced hypophagia, effects either maintained or even accentuated by the lard diet but counteracted by the fish diet. The OvxL group developed obesity and hyperleptinemia. Regarding components of hypothalamic serotonergic system, both ovariectomy alone or combined with the fish diet increased 5-HT2C expression while the lard diet reduced 5-HT1B mRNA. Ovariectomy increased the anxiety index, as derived from the elevated plus maze test, while both high-fat groups showed normalization of this index. In the forced swimming test, ovariectomy allied to high-lard diet, but not to fish-oil diet, reduced the latency to immobility, indicating vulnerability to a depressive-like state. Linear regression analysis showed hippocampal AgRP to be negatively associated with the anxiety index and hypothalamic AgRP to be positively associated with the latency to immobility. These AgRp gene expression associations are indicative of a beneficial involvement of this neuropeptide on both depression and anxiety measures. The present findings demonstrate metabolic, neurochemical and behavioral alterations after ovaries removal and highlight a positive effect of high-fat feeding on the anxiety-like behavior shown by ovariectomized animals. Since the polyunsaturated ômega-3 intake (fish diet), unlike the saturated fat intake (lard diet), failed to induce deleterious metabolic or neurochemical consequences, further studies are needed focusing on the potential of this dietary component as an adjuvant anxiolytic agent after menopause.

Maternal consumption of green tea extract during pregnancy and lactation alters offspring's metabolism in rats.

INTRODUCTION: Green tea extract has anti-inflammatory and antioxidant effects which improve dyslipidemia and decrease adipose tissue depots associated with hyperlipidic diet consumption. OBJECTIVE: To evaluate the effect of green tea extract consumption by rats during pregnancy and lactation on the metabolism of their offspring that received control or high-fat diet with water during 10 weeks after weaning. METHODS: Wistar rats received water (W) or green tea extract diluted in water (G) (400 mg/kg body weight/day), and control diet (10 animals in W and G groups) during pregnancy and lactation. After weaning, offspring received water and a control (CW) or a high-fat diet (HW), for 10 weeks. One week before the end of treatment, oral glucose tolerance test was performed. The animals were euthanized and the samples were collected for biochemical, hormonal and antioxidant enzymes activity analyses. In addition, IL-10, TNF-α, IL-6, and IL-1ß were quantified by ELISA while p-NF-κBp50 was analyzed by Western Blotting. Repeated Measures ANOVA, followed by Tukey's test were used to find differences between data (p < 0.05). RESULTS: The consumption of high-fat diet by rats for 10 weeks after weaning promoted hyperglycemia and hyperinsulinemia, and increased fat depots. The ingestion of a high-fat diet by the offspring of mothers who consumed green tea extract during pregnancy and lactation decreased the inflammatory cytokines in adipose tissue, while the ingestion of a control diet increased the same cytokines. CONCLUSION: Our results demonstrate that prenatal consumption of green tea associated with consumption of high-fat diet by offspring after weaning prevented inflammation. However, maternal consumption of the green tea extract induced a proinflammatory status in the adipose tissue of the adult offspring that received the control diet after weaning.