Resistance and Aerobic Training Were Effective in Activating Different Markers of the Browning Process in Obesity.

Lifestyle changes regarding diet composition and exercise training have been widely used as a non-pharmacological clinical strategy in the treatment of obesity, a complex and difficult-to-control disease. Taking the potential of exercise in the browning process and in increasing thermogenesis into account, the aim of this paper was to evaluate the effect of resistance, aerobic, and combination training on markers of browning of white adipose tissue from rats with obesity who were switched to a balanced diet with normal calorie intake. Different types of training groups promote a reduction in the adipose tissue and delta mass compared to the sedentary high-fat diet group (HS). Interestingly, irisin in adipose tissues was higher in the resistance exercise (RE) and aerobic exercise (AE) groups compared to control groups. Moreover, in adipose tissue, the fibroblast growth factor 21 (FGF21), coactivator 1 α (PGC1α), and peroxisome proliferator-activated receptor gamma (PPARγ) were higher in response to resistance training RE compared with the control groups, respectively. Additionally, uncoupling protein 1 (UCP1) showed higher levels in response to group AE compared to the HS group. In conclusion, the browning process in white adipose tissue responds differently toward different training exercise protocols, with resistance and aerobic training efficient in activating different biomarkers of the browning process, upregulating irisin, FGF21, PGC1α, PPARγ, and UCP1 in WAT, which together may suggest an improvement in the thermogenic process in the adipose tissue. Considering the experimental conditions of the present investigation, we suggest future research to pave new avenues to be applied in clinical practices to combat obesity.

The relationship between serum fatty acids and depressive symptoms in obese adolescents.

Depression and obesity are highly prevalent and are considered inflammatory pathologies; in addition, they are also associated with dietary patterns including types of fatty acids (FA). Changes in the FA composition in the brain are determined by changes in the content and quality of dietary and serum FA. The aim of this study was to verify the relationships between serum-free FA, inflammatory processes and depressive symptoms in obese adolescents. This was a cross-sectional study that analysed a database composed of 138 post-pubertal adolescents. Data regarding the depressive symptoms, body composition, glucose metabolism, lipid profile, FA profile, leptin concentration, as well as adiponectin, IL-A, IL-6, IL-10, TNF-α, C-reactive protein and plasminogen activator inhibitor-1 levels of the subjects were collected. A total of 54·6 % of the adolescents presented with depressive symptoms, and there were positive correlations between depressive symptoms and serum saturated fatty acids (SFA) content, body fat, and inflammatory adipokines, such as leptin, IL-6, and the leptin/adiponectin ratio. Moreover, the content of n-3 polyunsaturated fatty acids (PUFA) was negatively correlated with depressive symptoms, suggesting that eicosatrienoic acid (C20:2n6) and dihomo-γ-linolenic acid (C20:3n-6) are independently associated with depressive symptom scores and can be critical predictors of poor mental health in humans. These results point to the relationship between SFA and depressive symptoms in obese adolescents. However, longitudinal studies are needed to confirm the causality between dietary SFA and depression in obese individuals.

Aerobic exercise training regulates serum extracellular vesicle miRNAs linked to obesity to promote their beneficial effects in mice.

There is a growing body of evidence that extracellular vesicles (EVs) and their cargo of RNA, DNA, and protein are released in the circulation with exercise and might mediate interorgan communication. C57BL6/J male mice were subjected to diet-induced obesity and aerobic training on a treadmill for 8 wk. The effect of aerobic training was evaluated in the liver, muscle, kidney, and white/brown adipose tissue. To provide new mechanistic insight, we profiled miRNA from serum EVs of obese and obese trained mice. We demonstrate that aerobic training changes the circulating EV miRNA profile of obese mice, including decreases in miR-122, miR-192, and miR-22 levels. Circulating miRNA levels were associated with miRNA levels in mouse liver white adipose tissue (WAT). In WAT, aerobically trained obese mice showed reduced adipocyte hypertrophy and increased the number of smaller adipocytes and the expression of Cebpa, Pparg, Fabp4 (adipogenesis markers), and ATP-citrate lyase enzyme activity. Importantly, miR-22 levels negatively correlated with the expression of adipogenesis and insulin sensitivity markers. In the liver, aerobic training reverted obesity-induced steatohepatitis, and steatosis score and Pparg expression were negatively correlated with miR-122 levels. The prometabolic effects of aerobic exercise in obesity possibly involve EV miRNAs, which might be involved in communication between liver and WAT. Our data provide significant evidence demonstrating that aerobic training exercise-induced EVs mediate the effect of exercise on adipose tissue metabolism.

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.

Skeletal muscles induce recruitment of Ly6C+ macrophage subtypes and release inflammatory cytokines 3 days after downhill exercise.

Macrophages are one of the most versatile cells of the immune system that can express distinct subtypes and functions depending on the physiological challenge. After skeletal muscle damage, inflammatory macrophage subtypes aid muscles to regenerate and are implicated in physical training adaption. Based on this information, this study aimed to evaluate two classic mice macrophage subtypes and determine whether some inflammatory cytokines might be involved in the muscle adaption process after exercise. For this purpose, mice were exposed to an intermittent experimental protocol of downhill exercise (18 bouts of running, each bout 5 min with a 2-min rest interval, slope -16°) and were euthanized before [control (CTRL)] and 1, 2 (D2), and 3 (D3) days after exercise. After euthanasia, the triceps brachii was harvested and submitted to protein extraction, immunostaining, and mononuclear digestion procedures. The muscle size, macrophage accumulation, and cytokines were determined. We observed an increase in the Ly6C+ macrophage subtype (P ≤ 0.05) in D2 and D3 compared with CTRL, as well as a significant inverse correlation coefficient (-0.52; P ≤ 0.05) between Ly6C+ and Ly6C- macrophage subtypes. Moreover, we also observed elevation in several cytokines (IL-1ß, IFN-γ, TNF-α, IL-6, and IL-13) at D3, although not IL-4, which tended to decrease at this time point (P = 0.06). Downhill exercises preferentially recruited Ly6C+ macrophages with important proinflammatory cytokine elevation at D3. Moreover, despite the elevation of several cytokines involved with myogenesis, an increase in IL-6 and IL-13, which potentially involve muscle adaption training after acute exercise, was also observed.

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.

Polyphenols-Rich Fruit (Euterpe edulis Mart.) Prevents Peripheral Inflammatory Pathway Activation by the Short-Term High-Fat Diet.

Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage.

Diet Supplemented with Chia Flour did not Modified the Inflammatory Process and Tumor Development in Wistar Rats Inoculated with Walker 256 Cells.

Chia seed (Salvia hispanica L.) contains high amounts of n-3 α-linolenic acid (ALA) and has been associated with many health benefits. The aim of the present study was to evaluate the AIN-93 diet supplemented by chia flour on cancer-cachexia development and tissues inflammatory response. Wistar rats at 30 days old were treated with control diet or diet supplemented with chia flour for eight weeks. After this period, half of the animals in each diet group were inoculated with Walker 256 tumor cells. On the 14th day after tumor inoculation, the animals were euthanized and white adipose tissue depots, liver, gastrocnemius muscle, and tumor were removed. The tumor weight was higher and IL-10 content was lower in chia flour group. The tumor bearing did not modify the cytokines content in gastrocnemius muscle, retroperitoneal and epididymal adipose tissue, however, it decreased IL-1ß and TNF-α content in liver, and IL6R and IL-10R protein content in mesenteric adipose tissue. In conclusion, our results demonstrated that supplementation with chia flour did not prevent the tumor bearing effects in Walker 256 model.

Effect of fructo-oligosaccharide supplementation in soya beverage on the intestinal absorption of calcium and iron in newly weaned rats.

Studies have shown the positive effects of prebiotics on the intestinal absorption of Ca and Fe. The present study evaluated the effect of fructo-oligosaccharide (FOS) supplementation in soya beverage (SB) on absorption mechanisms of Ca and Fe in recently weaned rats. Male Wistar rats were divided into four groups: lactose-free cows' milk (CM), lactose-free CM with FOS (0·8 g/100 ml) (CMF), SB and soya beverage with FOS (0·8 g/100 ml) (SBF). These rats were euthanised after 1 week of treatment. Organ weight, pH of the caecal content and absorption mechanisms of Ca and Fe were evaluated. The results showed that the weight of the caecal contents increased in the CMF and SBF groups, and the pH of the caecal contents was lower in these groups. The Hb levels of the CMF and SB groups were higher when compared with that of the CM group and lower in relation to the SBF group. The apparent Ca and Fe absorption and apparent Ca retention in the CM group were higher when compared with the SB group, whereas in the CMF group, they were higher in relation to the SBF group. Divalent metal transporter 1 (DMT1) protein expression in the duodenum was higher in the SBF group than in the SB and CMF groups. SB resulted in lower intestinal Ca absorption and higher Hb concentration, despite the lower apparent Fe absorption in relation to CM. Supplementation with FOS provided beneficial effects on Hb and DMT1 protein expression in the duodenum, in addition to improving the absorption process.

The Long-Term Impact of High Levels of Alpha-Melanocyte-Stimulating Hormone in Energy Balance Among Obese Adolescents.

BACKGROUND: Deregulation of orexigenic and anorexigenic pathways occurs among adolescents with obesity. Alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis and an important anorexigenic neuropeptide in the control of energy balance and thermogenesis. However, it was not well explored if α-MSH can modulate long-term weight loss therapy responses in a dependent manner according to its concentration. Our hypothesis is that a high α-MSH concentration at baseline promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents. METHODS: One hundred ten post-pubertal obese adolescents (body mass index >95th percentile) were submitted to 1 year of interdisciplinary therapy (clinical, nutritional, psychological, physical exercise, and physiotherapy support). Body composition and plasma levels of α-MSH, neuropeptide Y (NPY), melanin-concentrating hormone, and agouti-related peptide (AgRP) were measured before and after therapy. The volunteers were grouped on the basis of Tertiles of α-MSH concentration: Low (<0.75 ng/mL), Medium (≤0.76 to ≥1.57 ng/mL), and High (>1.57 ng/mL). Significance was set as p < 0.05. RESULTS: The treatment promoted a significant improvement in body adiposity and fat free mass for all groups. It is important to note that only in the high α-MSH group, a significant increase of the α-MSH/NPY ratio and decrease NPY/AgRP ratio post treatment were observed. CONCLUSION: The high α-MSH concentration promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents following long-term weight loss therapy and this is important in clinical practice.

Commercial Fucoidans from Fucus vesiculosus Can Be Grouped into Antiadipogenic and Adipogenic Agents.

Fucus vesiculosus is a brown seaweed used in the treatment of obesity. This seaweed synthesizes various bioactive molecules, one of them being a sulfated polysaccharide known as fucoidan (FF). This polymer can easily be found commercially, and has antiadipogenic and lipolytic activity. Using differential precipitation with acetone, we obtained four fucoidan-rich fractions (F0.5/F0.9/F1.1/F2.0) from FF. These fractions contain different proportions of fucose:glucuronic acid:galactose:xylose:sulfate, and also showed different electrophoretic mobility and antioxidant activity. Using 3T3-L1 adipocytes, we found that all samples had lipolytic action, especially F2.0, which tripled the amount of glycerol in the cellular medium. Moreover, we observed that FF, F1.0, and F2.0 have antiadipogenic activity, as they inhibited the oil red staining by cells at 40%, 40%, and 50%, respectively. In addition, they decreased the expression of key proteins of adipogenic differentiation (C/EBPα, C/EBPß, and PPARγ). However, F0.5 and F0.9 stimulated the oil red staining at 80% and increased the expression of these proteins. Therefore, these fucoidan fractions have an adipogenic effect. Overall, the data show that F2.0 has great potential to be used as an agent against obesity as it displays better antioxidant, lipolytic and antiadipogenic activities than the other fucoidan fractions that we tested.

The effects of exercise training associated with low-level laser therapy on biomarkers of adipose tissue transdifferentiation in obese women.

Investigations suggest the benefits of low-level laser therapy (LLLT) to improve noninvasive body contouring treatments, inflammation, insulin resistance and to reduce body fat. However, the mechanism for such potential effects in association with exercise training (ET) and possible implications in browning adiposity processes remains unclear. Forty-nine obese women were involved, aged between 20 and 40 years with a body mass index (BMI) of 30-40 kg/m2. The volunteers were divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of exercise training and phototherapy applications post exercise for 4 months, with three sessions/week. Body composition, lipid profile, insulin resistance, atrial natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and an increase in WNT5 signaling. In addition, it was possible to observe a higher magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the Phototherapy group. In the present investigation, it was demonstrated that exercise training associated with LLLT promotes an improvement in body composition and inflammatory processes as previously demonstrated. The Phototherapy group especially presented positive modifications of WNT5 signaling, FGF-21, and ANP, possible biomarkers associated with browning adiposity processes. This suggests that this kind of intervention promotes results applicable in clinical practice to control obesity and related comorbidities.

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.

The Secretory Leukocyte Protease Inhibitor mRNA expression is involved with inflammatory control after downhill exercise in the triceps brachii intermediary head in Wistar rats.

After severe skeletal muscle damage, communication between inflammatory macrophages, myogenic cells, and modulatory secretion factors is essential to induce re-establishment of skeletal muscle structure. To analyze when characteristic gene expression of macrophages, myogenic cells, and SLPI are modulated after an exercise-induced muscle damage (EIMD) downhill protocol. Twenty-six rats were exposed to an experimental protocol of exercise and euthanized before (CTRL), immediately after (G0), and 24 (G24) and 48 (G48) hours after the exercise. After euthanasia, the Triceps brachii were dissected and analyzed by enzyme-linked immunosorbent assay and real time polymerase chain reaction. The CD68 expression was higher in the G24 when compared with all groups (p value < 0.05), whereas the CD163 was inhibited compared with G0 (p value < 0.05). MyoD and Myogenin were higher in the G24 when compared with G0 and G48 (p value < 0.05). The mRNA Secretory Leukocyte Protease Inhibitor (SLPI) was higher in the G48 when compared with the CTRL and G0 (p value < 0.05). IL-6 and TNF-α cytokines did not significantly change, but IL-10 presented a trend to be lower in the G0 when compared with G24 (p value = 0.054). A significant negative correlation was observed between CD68/CD163 (C.C = -0.71) and positive correlations between CD68/Myogenin (C.C = 0.65); MyoD/Myogenin (C.C = 0.72); IL-10/MyoD (C.C = 0.46), IL-10/MYOGENIN (C.C = 0.59); and IL-6/IL-10 (C.C = 0.64). A higher expression of CD68, concomitant with an elevation in MyoD and Myogenin 24 h after exercise, along with some correlations, suggests macrophage communication with myogenic cells independent of CD163 elevation. Additionally, the reestablishment of IL-10 in 24 h with the SLPI increased until 48 h indicate that these molecules are involved with anti-inflammatory transition after downhill exercise in the TBIH of Wistar rats.

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.

Effects of prebiotic supplementation on the expression of proteins regulating iron absorption in anaemic growing rats.

Prebiotics may increase intestinal Fe absorption in anaemic growing rats. The present study evaluated the effects of high-performance (HP) inulin and oligofructose on factors that regulate Fe absorption in anaemic rats during the growth phase. Male Wistar rats aged 21 d of age were fed AIN-93G ration without Fe for 2 weeks to induce Fe-deficiency anaemia. The rats were fed on day 35 a control diet, or a diet with 10 % HP inulin, or a diet with 10 % oligofructose, without Fe supplementation. The animals were euthanised after 2 weeks, and segments of the duodenum, caecum, colon and liver were removed. The expression levels of proteins in the intestinal segments were assessed using Western blotting. The levels of serum, urine and liver hepcidin and the concentrations of IL-10, IL-6 and TNF-α in the caecum, colon and liver were measured using the ELISA test. HP inulin increased the expression of the divalent metal transporter 1 protein in the caecum by 162 % (P= 0·04), and the expression of duodenal cytochrome b reductase in the colon by 136 % (P= 0·02). Oligofructose decreased the expression of the protein ferroportin in the duodenum (P= 0·02), the concentrations of IL-10 (P= 0·044), IL-6 (P= 0·036) and TNF-α (P= 0·004) in the caecum, as well as the level of urinary hepcidin (P< 0·001). These results indicate that prebiotics may interfere with the expression of various intestinal proteins and systemic factors involved in the regulation of intestinal Fe absorption in anaemic rats during the growth phase.

Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats.

We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1ß, IL-6, IL-10, TNF-α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p < 0.01). Hypothalamic malate dehydrogenase activity was reduced when compared with control (p < 0.05). In addition, pro-inflammatory cytokine levels were unchanged. Therefore, our results demonstrate that doxorubicin leads to an impairment of \hypothalamic energy metabolism, but do not affect the inflammatory pathway. SIGNIFICANCE PARAGRAPH: The hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term.

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.

Ginkgo biloba extract improves insulin signaling and attenuates inflammation in retroperitoneal adipose tissue depot of obese rats.

Due to the high incidence and severity of obesity and its related disorders, it is highly desirable to develop new strategies to treat or even to prevent its development. We have previously described that Ginkgo biloba extract (GbE) improved insulin resistance and reduced body weight gain of obese rats. In the present study we aimed to evaluate the effect of GbE on both inflammatory cascade and insulin signaling in retroperitoneal fat depot of diet-induced obese rats. Rats were fed with high fat diet for 2 months and thereafter treated for 14 days with 500 mg/kg of GbE. Rats were then euthanized and samples from retroperitoneal fat depot were used for western blotting, RT-PCR, and ELISA experiments. The GbE treatment promoted a significant reduction on both food/energy intake and body weight gain in comparison to the nontreated obese rats. In addition, a significant increase of both Adipo R1 and IL-10 gene expressions and IR and Akt phosphorylation was also observed, while NF-κB p65 phosphorylation and TNF-α levels were significantly reduced. Our data suggest that GbE might have potential as a therapy to treat obesity-related metabolic diseases, with special interest to treat obese subjects resistant to adhere to a nutritional education program.

Effect of a 12-Week Low vs. High Intensity Aerobic Exercise Training on Appetite-Regulating Hormones in Obese Adolescents: A Randomized Exercise Intervention Study.

Little is known about how the intensity of aerobic training influences appetite-regulating hormones in obese adolescents. Our goal was to assess the effect of low and high intensity aerobic trainings on food intake and appetite-regulating hormones in obese adolescents. Forty three obese adolescents (age: 13-18y, BMI: 34.48 ± 3.94 kg/m2) were randomized into high intensity training (HIT; n = 20) or low intensity training (LIT; n = 23) groups for 12 weeks. All participants also received the same nutritional, psychological and clinical counseling. Pre- and postintervention energy intake (EI) and circulating levels of insulin, leptin, peptide YY3-36 (PYY3-36) and ghrelin were measured. Adolescents in the HIT showed a reduction in total EI and an increase in PYY3-36 (p < .05). Aerobic exercise training performed at ventilatory threshold 1 intensity, reduced EI and augmented PYY3-36 in obese adolescents, compared with LIT. The data suggest that HIT and LIT have differential effects in the regulation of appetite signals and subsequent EI in obese adolescents.