Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression.

Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10-14), guanosine (FDR = 3.001 × 10-14), proline (FDR = 1.430 × 10-6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.

Proteome analysis indicates participation of the dorsal hippocampal formation in fear-motivated memory in a time-dependent manner.

Our previous behavioral and molecular data indicate a central role of the dorsal hippocampal formation (dHF) in recent conditioned lick suppression memory. The purpose of this study was to investigate the role of the dHF in recent and remote memory of conditioned lick suppression employing proteomic analysis. Two or 40 days after conditioning, the rats were subjected to a retention test and were then euthanized after 24 hr for dHF collection. We identified 1,165 proteins and quantified 265 proteins. Upregulation of five proteins and downregulation of 21 proteins were found on postconditioning Day 2. Additionally, four proteins were upregulated and 21 proteins were downregulated on postconditioning Day 40. Integrated pathway analysis of the proteomics data indicated changes in the myelin sheath, neuron generation and differentiation, regulation of neurogenesis and synaptic vesicle transport, axonal development, and the growth cone. Our findings provide further support for the role of the dHF in conditioned lick suppression memory and novel insights into the molecular changes that are correlated with recent and remote memory in the dHF, which may be a target for cognitive enhancers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ginkgo biloba Extract Stimulates Adipogenesis in 3T3-L1 Preadipocytes.

Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPß levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes' markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected.

Thyroid axis hormones and anthropometric recovery of children/adolescents with overweight/obesity: A scoping review.

Introduction: Thyroid hormones exert multiple physiological effects essential to the maintenance of basal metabolic rate (BMR), adaptive thermogenesis, fat metabolism, growth, and appetite. The links between obesity and the hormones of the thyroid axis, i.e., triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH), are still controversial, especially when considering children and adolescents. This population has high rates of overweight and obesity and several treatment approaches, including nutritional, psychological, and physical exercise interventions have been used. Understanding the importance of the hormones of the thyroid axis in the recovery from overweight and obesity may help directing measures to the maintenance of a healthy body composition. The present scoping review was carried out to analyze studies evaluating these hormonal levels throughout interventions directed at treating overweight and obesity in children and adolescents. The main purpose was to ascertain whether the hormones levels vary during weight loss. Methods: We selected for analysis 19 studies published between 1999 and 2022. Results: Most of the studies showed that changes in different anthropometric indicators, in response to the multidisciplinary interventions, correlated positively with free T3 (fT3), total T3 (TT3), and TSH. With respect to free T4 (fT4) and total T4 (TT4). Discussion: The most common finding was of unchanged levels and, hence, no significant association with weight loss. Moreover, thyroxine supplementation has failed to affect the response to the interventions. Further studies are necessary to elucidate the relevance of the variations in hormone levels to the establishment of overweight/obesity and to the recovery from these conditions in children/adolescents. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020203359.

Dose- and Time-Dependent Effects of Oleate on Mitochondrial Fusion/Fission Proteins and Cell Viability in HepG2 Cells: Comparison with Palmitate Effects.

Mitochondrial impairments in dynamic behavior (fusion/fission balance) associated with mitochondrial dysfunction play a key role in cell lipotoxicity and lipid-induced metabolic diseases. The present work aimed to evaluate dose- and time-dependent effects of the monounsaturated fatty acid oleate on mitochondrial fusion/fission proteins in comparison with the saturated fatty acid palmitate in hepatic cells. To this end, HepG-2 cells were treated with 0, 10 µM, 50 µM, 100 µM, 250 µM or 500 µM of either oleate or palmitate for 8 or 24 h. Cell viability and lipid accumulation were evaluated to assess lipotoxicity. Mitochondrial markers of fusion (mitofusin 2, MFN2) and fission (dynamin-related protein 1, DRP1) processes were evaluated by Western blot analysis. After 8 h, the highest dose of oleate induced a decrease in DRP1 content without changes in MFN2 content in association with cell viability maintenance, whereas palmitate induced a decrease in cell viability associated with a decrease mainly in MFN2 content. After 24 h, oleate induced MFN2 increase, whereas palmitate induced DRP1 increase associated with a higher decrease in cell viability with high doses compared to oleate. This finding could be useful to understand the role of mitochondria in the protective effects of oleate as a bioactive compound.

Preliminary evidence of acylated ghrelin association with depression severity in postmenopausal women.

We have previously shown increased depression and anxiety scores in postmenopausal overweight women, when compared to overweight premenopausal women. The mechanisms responsible for these alterations are not understood. Although ghrelin involvement in mood modulation has been suggested, its role is still ambiguous and has not been evaluated in postmenopause. Here we investigated the association of ghrelin with depression and anxiety symptoms in postmenopausal women. Fifty-five postmenopausal women with depression symptoms, who were not in use of hormones or antidepressants, were included in the study. Depression symptoms were evaluated by Beck's Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) and anxiety symptoms were evaluated by Beck's Anxiety Inventory (BAI). Women were allocated into three groups, according to BDI classification of mild, moderate, or severe depression symptoms. Anthropometric, biochemical and hormonal parameters were analyzed. Total and acylated ghrelin levels were higher in the severe depression than in the mild depression group. Multivariate regression analyses showed positive associations of BDI scores with acylated ghrelin and BMI, and of PHQ-9 scores with acylated ghrelin and homeostasis model assessment of insulin resistance (HOMA-IR). BAI scores associated positively with waist-to-hip ratio. To the best of our knowledge, this is the first demonstration of an association between acylated ghrelin and the severity of depression symptoms in postmenopausal women. This association may reflect either a physiological response aimed at fighting against depression symptoms or a causal factor of this mental disorder.

Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet.

Menopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17ß-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-ß indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-ß index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono-Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono-Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono-Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.

Ginkgo biloba Extract (GbE) Restores Serotonin and Leptin Receptor Levels and Plays an Antioxidative Role in the Hippocampus of Ovariectomized Rats.

Since Ginkgo biloba extract (GbE) was reported to improve the hypothalamic serotonergic system of ovariectomized (OVX) rats, the present study aimed to verify the GbE effects on hippocampal oxidative stress, inflammation, and levels of the serotonin transporter (5-HTT), and both the serotonin (5-HT1A, 5-HT1B) and leptin receptors of OVX rats. Two-month-old female Wistar rats had their ovaries surgically removed (OVX) or not (SHAM). After 60 days, OVX rats were gavaged daily with GbE 500 mg kg-1 (OVX+GbE), while SHAM and OVX groups received saline 0.9% (vehicle) for 14 days. Rats were then euthanized, and hippocampi were collected. Both 5-HT1A and 5-HT1B levels were significantly reduced in OVX rats compared to SHAM rats, while 5-HT1A was higher in OVX+GbE rats in comparison to OVX rats. Similarly, LepR levels were increased in OVX+GbE rats compared to OVX rats, reaching similar levels to SHAM rats. Superoxide dismutase activity increased in OVX rats in relation to SHAM rats, which was restored to SHAM levels by GbE treatment. Additionally, GbE significantly increased the glutathione peroxidase activity in comparison to the SHAM group. No differences were observed either in catalase activity or in the levels of 5-HTT, PKCα, TLR-4, NF-κBp50, ERK, and CREB. In summary, our results show a potential effect of GbE on hippocampal pathways involved in feeding behavior, and thus, they suggest that GbE activity might improve menopausal-related hippocampal disorders, offering an alternative therapeutic tool particularly for women to whom hormone replacement therapy may be contraindicated.

Ginkgo biloba extract (GbE) attenuates obesity and anxious/depressive-like behaviours induced by ovariectomy.

While several pieces of evidence link obesity and mood disorders in menopause, the mechanisms involved are not yet fully understood. We have previously demonstrated that Ginkgo biloba extract (GbE) both attenuated diet-induced obesity of male rats and restored serotonin-induced hypophagia in ovariectomized female rats. The present study aimed at exploring whether GbE treatment ameliorates ovariectomy-related obesity and anxious/depressive-like behaviours. Wistar female rats were either ovariectomized (OVX) or sham-operated (Sham). After 2 months, either 500 mg/kg of GbE or vehicle were administered daily by gavage for 14 days. Anxious/depressive-like behaviours were assessed by the Elevated Plus Maze and the Forced Swim Tests, respectively. Ovariectomy caused high visceral adiposity, hyperleptinemia, and hypercholesterolemia, and increased the anxiety index (p = 0.048 vs. Sham + GbE) while it decreased the latency to immobility (p = 0.004 vs. Sham). GbE treatment in OVX rats improved body composition, adiponectin levels and blood lipid profile. It also reduced the anxiety index (p = 0.004) and increased the latency to immobility (p = 0.003) of OVX rats. Linear regression analysis demonstrated that leptin (p = 0.047) and total cholesterol levels (p = 0.022) were associated with anxious-like behaviours while body adiposity (p = 0.00005) was strongly associated with depressive-like behaviours. The results showed that GbE therapy was effective in attenuating the deleterious effects of ovariectomy on body composition, lipid profile, and anxious/depressive-like behaviours. Further studies are warranted to better understand the therapeutic potential of GbE in menopause.

Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.

Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep. A literature search was performed on the PubMed, Scopus, and ScienceDirect databases, including only randomized, placebo-controlled trials published in English between 2005 and 2019. The methodological quality of the trials was assessed by the Jadad scale. Of the 25 eligible articles, eight met the inclusion criteria. They addressed the intake of milk or cherry juice in children, adults, and elderly subjects and evaluated sleep quality by questionnaires, sleep diary, actigraphy, or polysomnography. The analysis of the studies presented limitations, including lack of homogeneity of treatment dosage and duration. Nonetheless, the results indicated that the consumption of milk and sour cherries, sources of melatonin, may improve sleep quality in humans. These results pointed out to the potential suitability of food sources of melatonin as adjuvants in the prevention and treatment of sleep disorders. Further studies are necessary to better ascertain the aspects relevant to their use.

Neuroendocrine Control, Inflammation, and Psychological Aspects After Interdisciplinary Therapy in Obese Women.

Obesity is a chronic and multifactorial disease promoted by positive energy balance. The objective was to evaluate the effects of interdisciplinary therapy in the neuroendocrine control of food intake, inflammatory markers, and psychological aspects in obese women. Forty-seven obese women (43.32±5.82 years, 34.86±3.08 kg/m2), aged 30-50 years, participated in an interdisciplinary lifestyle change therapy, consisting of nutritional counseling, physical exercises, and psychological therapy for 36 weeks. After the long-term therapy, there was a decrease in body weight (Δ -5.36 kg), BMI (Δ -2.01 kg/m2), abdominal (Δ -9.09 cm), hip (Δ -5.03 cm), and thigh (Δ -5.07 cm) perimeters. There was also a significant improvement in body composition, with an increase in fat-free mass (Δ 1.60%) and reduction of body fat (Δ -3.74 kg). The therapy proposed also provided an improvement in depression scores (Δ -6.63), anxiety (Δ -4.07), body image (Δ -25.25), and binge eating (Δ -5.25). There was a significant reduction in serum levels of leptin (Δ -15.62 ng/ml). The interdisciplinary therapy was able to provide both, physical and psychological benefits in energy balance, which enables the use of this model as a feasible clinical strategy for the treatment of obesity.

Chia flour (Salvia hispanica L.) did not improve the deleterious aspects of hyperlipidic diet ingestion on glucose metabolism, but worsened glycaemia in mice.

Obesity is mainly caused by intake of a high-fat diet and sedentarism, and is considered a public health issue worldwide. Increased intestinal permeability may favour endotoxaemia generated by lipopolysaccharides, a substance present in the cell membrane of Gram-negative bacteria, and, consequently, an increase in systemic inflammation and metabolic diseases. In contrast (On the other hand), consumption of a healthy diet can help in the prevention and treatment of metabolic syndrome. In this way, chia seeds (Salvia hispanica L.), rich in polyunsaturated fatty acids, may present an anti-inflammatory role. In addition, chia is rich in antioxidants like caffeic and gallic acid and fiber. However, few studies have investigated the relationship between chia seeds, inflammatory mechanisms and intestinal permeability. Therefore, the aim of this study was to analyse the effects of chia administration on metabolism in obese mice. Swiss mice were fed a hyperlipidic diet either supplemented with or without 3% chia flour for 16 weeks. The results showed that supplementation could not reduce the deleterious effects of the lipid-rich diet in terms of body composition, glucose intolerance and activity of antioxidants enzymes in the liver. In addition, supplementation with chia in the control diet decreased the amount of occludin in the intestinal colon. In conclusion, although chia did not improve metabolic parameters it seemed to restore the intestinal barriers integrity. The beneficial effects of chia seem to be dependent of the quantity used, since our data conflict with those in the literature; however, it is important to note that other studies, unlike our protocol, used chia in the form of seeds or oil, and not flour.

Age and leptinemia association with anxiety and depression symptoms in overweight middle-aged women.

OBJECTIVE: The aim of the study was to investigate the effect of menopause and of postmenopausal stages on depression and anxiety symptoms, and whether these symptoms associate with anthropometric, metabolic, and hormonal parameters in midlife women. METHODS: Postmenopausal women (age 50-65), either at early (EPM, n=33) or late (LPM, n = 23) postmenopause, and 23 premenopausal controls (PreM, age 40-50), matched for BMI with the PM groups, were studied. Blood biochemical and hormonal determinations, bioimpedance anthropometry, and depression and anxiety symptoms (Beck's depression [BDI] and anxiety [BAI] inventories) were conducted. RESULTS: The BAI score was higher in both PM groups than in the PreM group. In contrast, only the LPM group showed a significantly elevated BDI score. All groups presented overweight and abdominal obesity, having similar BMI and waist/hip ratio values. Both PM groups showed insulin resistance, whereas only the LPM group presented decreased skeletal muscle mass and basal metabolic rate. Correlation analysis, including all 79 middle-aged women, showed age, percentage body fat, waist/hip ratio, and leptinemia to correlate positively with the anxiety and depression scores. Multivariate regression showed leptin and age to associate positively with depressive- and anxious-like symptoms. CONCLUSIONS: Postmenopausal women presented impaired body composition, energy expenditure, insulin sensitivity, and mental symptoms, in comparison to similarly overweight premenopausal women. Among all the overweight midlife women, these symptoms were more strongly associated with age and leptin levels than with reproductive aging itself. The data indicate that, among overweight middle-aged women with abdominal obesity, the aging process and the development of leptin resistance are associated with impairment of mental health.

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.

Effect of the consumption of green tea extract during pregnancy and lactation on metabolism of mothers and 28d-old offspring.

The objective was to investigate the effects of the maternal consumption of the green tea extract during pregnancy and lactation on mothers and offspring metabolism. The female Wistar rats, on the first day of pregnancy until the end of lactation, was divided into groups: MC- received water and ME- received green tea extract (400 mg/kg body weight/day), both ingested control diet. After lactation, at day 28th post-partum, the mothers and pups from each mother were euthanized and composed the groups: FC- pup from mother received water and FE- pup from mother received green tea extract. The ME group increased IL-10/TNF-α ratio and IL-1ß content in the mesenteric and IL-1ß content in retroperitoneal adipose tissues, and decreased catalase activity. The FE group decreased the retroperitoneal adipose tissue relative weight and SOD activity, but increased adiponectin, LPS, IL-10 and IL-6 content and IL-10/TNF-α ratio in retroperitoneal, IL-10 and TNF-α content in gonadal, and IL-6 content in mesenteric adipose tissues. In summary, the maternal consumption of green tea extract associated with control diet ingestion during pregnancy and lactation altered the inflammatory status of mothers and 28d-old offspring. These data elucidate the effects of green tea during pregnancy and lactation on maternal and offspring metabolism.

Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.

Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.

Gender-specific effects of intrauterine growth restriction on the adipose tissue of adult rats: a proteomic approach.

BACKGROUND: Intrauterine growth restriction (IUGR) may program metabolic alterations affecting physiological functions and lead to diseases in later life. The adipose tissue is an important organ influencing energy homeostasis. The present study was aimed at exploring the consequences of IUGR on the retroperitoneal adipose tissue of adult male and female rats, using a proteomic approach. METHODS AND RESULTS: Pregnant Wistar rats were fed with balanced chow, either ad libitum (control group) or restricted to 50 % of control intake (restricted group) during the whole gestation. The offspring were weaned to ad libitum chow and studied at 4 months of age. Retroperitoneal fat was analyzed by two-dimensional gel electrophoresis followed by mass spectrometry. Both male and female restricted groups had low body weight at birth and at weaning but normal body weight at adulthood. The restricted males had normal fat pads weight and serum glucose levels, with a trend to hyperinsulinemia. The restricted females had increased fat pads weight with normal glucose and insulin levels. The restricted males showed up-regulated levels of proteasome subunit α type 3, branched-chain-amino-acid aminotransferase, elongation 1- alpha 1, fatty acid synthase levels, cytosolic malate dehydrogenase and ATP synthase subunit alpha. These alterations point to increased proteolysis and lipogenesis rates and favoring of ATP generation. The restricted females showed down-regulated levels of L-lactate dehydrogenase perilipin-1, mitochondrial branched-chain alpha-keto acid dehydrogenase E1, and transketolase. These findings suggest impairment of glycemic control, stimulation of lipolysis and inhibition of proteolysis, pentose phosphate pathway and lipogenesis rates. In both genders, several proteins involved in oxidative stress and inflammation were affected, in a pattern compatible with impairment of these responses. CONCLUSIONS: The proteomic analysis of adipose tissue showed that, although IUGR affected pathways of substrate and energy metabolism in both males and females, important gender differences were evident. While IUGR males displayed alterations pointing to a predisposition to later development of obesity, the alterations observed in IUGR females pointed to a metabolic status of established obesity, in agreement with their increased fat pads mass.

Maternal Supplementation with Oligofructose (10%) during Pregnancy and Lactation Leads to Increased Pro-Inflammatory Status of the 21-D-Old Offspring.

Previously, we showed that oligofructose (10%) supplementation during pregnancy and lactation increased endotoxemia in 21-d-old pups. The present study evaluated the effect of 10% oligofructose diet supplementation during pregnancy and lactation in the presence or absence of hydrogenated vegetable fat on the pro-inflammatory status of 21-d-old offspring. On the first day of pregnancy, female Wistar rats were divided into the following groups: control diet (C), control diet supplemented with 10% oligofructose (CF), diet enriched with hydrogenated vegetable fat (T) or diet enriched with hydrogenated vegetable fat supplemented with 10% oligofructose (TF). Diets were maintained during pregnancy and lactation. Serum TNF-α (tumor necrosis factor alpha) was assessed using a specific kit. Protein expression was determined by Western Blotting, and the relative mRNA levels were analyzed by RT-PCR (real-time polymerase chain reaction). We observed that 10% oligofructose supplementation during pregnancy and lactation increased offspring's IL-6R (interleukin-6 receptor) mRNA levels in the liver and RET (retroperitoneal white adipose tissue) and decreased ADIPOR2 (adiponectin receptor 2) and ADIPOR1 (adiponectin receptor 1) gene expression in liver and EDL (extensor digital longus)/ SOL (soleus) muscles of CF group. Additionally, TF group presented with increased serum TNF-α, protein expression of p-NFκBp65 (phosphorylated form of nuclear factor kappa B p65 subunit) in liver and IL-6R mRNA levels in RET. These findings were accompanied by decreased levels of ADIPOR1 mRNA in the EDL and SOL muscles of the TF group. In conclusion, supplementing the dam's diet with 10% of oligofructose during pregnancy and lactation, independent of hydrogenated vegetable fat addition, contributes to the increased pro-inflammatory status of 21-d-old offspring, possibly through the activation of the TLR4 (toll like receptor 4) pathway.

A Hyperlipidic Diet Combined with Short-Term Ovariectomy Increases Adiposity and Hyperleptinemia and Decreases Cytokine Content in Mesenteric Adipose Tissue.

Four-week-old female Wistar rats were divided into two groups and fed a control diet (C) or a hyperlipidic diet (H) for 4 weeks. Rats from each group underwent ovariectomy (OVX) or sham surgery (SHAM). They received C or H for the next four weeks. The body weight gain (BW), food efficiency (FE), and carcass lipid content were higher in the OVX H than in the SHAM H. The OVX H exhibited a higher serum leptin level than other groups. IL-6, TNF-α, and IL-10 content of mesenteric (MES) adipose tissue was lower in the OVX H than in the OVX C. IL-6, TNF-α, and IL-10 content of retroperitoneal (RET) adipose tissue was lower in the SHAM H than in the SHAM C. The SHAM H showed decreased TG relative to the SHAM C. Similar results were obtained in relation to IL-6Rα, TNFR1, TLR-4, and MyD88 contents in the MES and RET white adipose tissue among the groups. A hyperlipidic diet for 8 weeks combined with short-term ovariectomy decreases the cytokine content of MES adipose tissues but increases BW, enhancing FE and elevating serum leptin levels. These suggest that the absence of estrogens promotes metabolic changes that may contribute to installation of a proinflammatory process induced by a hyperlipidic diet.