The futile creatine cycle and the synthesis of fatty acids in inguinal white adipose tissue from growing rats, submitted to a hypoprotein-hyperglycidic diet for 15 days.

The low-protein, high-carbohydrate (LPHC) diet administered to growing rats soon after weaning, for 15 days, promoted an increase in energy expenditure by uncoupling protein 1 (UCP1) in interscapular brown adipose tissue, and also due to the occurrence of the browning process in the perirenal white adipose tissue (periWAT). However, we believe that inguinal white adipose tissue (ingWAT) may also contribute to energy expenditure through other mechanisms. Therefore, the aim of this work is to investigate the presence of the futile creatine cycle, and the origin of lipids in ingWAT, since that tissue showed an increase in the lipids content in rats submitted to the LPHC diet for 15 days. We observed increases in creatine kinase and alkaline phosphatase activity in ingWAT, of the LPHC animals. The mitochondrial Nicotinamide adenine dinucleotide reduced/nicotinamide adenine dinucleotide oxidized ratio is lower in ingWAT of LPHC animals. In the LPHC animals treated with ß-guanidinopropionic acid, the extracellular uptake of creatine in ingWAT was lower, as was the rectal temperature. Regarding lipid metabolism, we observed that in ingWAT, lipolysis in vitro when stimulated with noradrenaline is lower, and there were no changes in baseline levels. In addition, increases in the activity of enzymes were also observed: malic, glucose-6-phosphate dehydrogenase, and ATP-citrate lyase, in addition to an increase in the PPARγ content. The results show the occurrence of the futile creatine cycle in ingWAT, and that the increase in the relative mass may be due to an increase in de novo fatty acid synthesis.

Introduction of high-fat and very-high-fat diets associated with fructose drink in critical development periods causes cardiovascular damage in rats at the beginning of adult life.

OBJECTIVES: Exposure to an obesogenic environment at critical stages of human development may lead to cardiovascular damage during early adulthood, such as left ventricular hypertrophy (LVH). The objective of this study is to investigate whether the consumption of diets with different levels of fat associated with fructose drink, introduced to newly weaned rats, leads to cardiovascular damage. METHODS: Male Wistar rats (age 21 d) were divided into the following groups: Control (C group) fed an American Institute of Nutrition 93G diet (16.3 % kcal of lipid); high-fat diet (HF group: 45% kcal of lipids), and very-high-fat diet (VHF group: 60% kcal of lipids). The HF and VHF groups also received a fructose solution (10%) for hydration. RESULTS: After 70 d, the animals in the HF and VHF groups presented with cardiovascular damage as a comorbidity of obesity, with increased creatine kinase-MB levels, high heart and left ventricle (LV) mass, and an increase in the LV:tibia ratio. The positive correlation was observed between serum leptin levels and LV mass. In addition, the signal transducer and activator of transcription 3 content in LV was lower. CONCLUSIONS: The administration of diets with different fat and carbohydrate contents associated with fructose drinks introduced to newly weaned rats leads to LVH during early adulthood. The data suggest that the change in leptin-signal transducer and activator of transcription 3 pathway signaling in the groups is related to the occurrence of LVH.

Acute supplementation of growing rats with Brazil nut flour increases hepatic lipid content but prevents oxidative damage in the liver.

Brazil nuts (BN) (Bertholletia excels, Bonpl.), are of great importance because of their nutritional properties and economic value. They can be consumed in natura or as flour (BNF). In this study, we evaluated the effects of BNF and BN intakes (Both 5% and 15%) on metabolic parameters of rats for 15 days. Serum Selenium (Se) levels were higher in BN-15% and BNF-15% groups. Lipid content was reduced in retroperitoneal and epididymal adipose tissues in all groups and in the BN-5% group in the liver. However, liver lipids increased in the BNF-15% group. The levels of carbonylated proteins and lipid peroxidation in the liver were not altered. The data reveal that the increase in hepatic lipids in the BNF-15% group probably occurred due to the high concentration of free fatty acids present in the flour. The Se bioavailability in the diet contributed to the preservation of the liver function in rats. PRACTICAL IMPLICATIONS: The consumption of BN is common in the population. However, changes in eating habits have led to a more frequent consumption of vegetable derivatives, such as drinks and oils. The cake residue generated after processing is still considered of high nutritional value, since it is a source of protein and minerals such as Se. Because of its low cost, the use of pie at the industrial level is becoming increasingly more interesting for the development of new products, and the Brazil nut flour (BNF) is considered a good option. Our study showed that just like BN, BNF can be a source of selenium for the body, although changes in lipid metabolism and physiological parameters can be observed depending on the amount used. We believe that the results of this investigation can be used to guide the development of new technologies and products containing BN.

High-fat diet and fructose drink introduced after weaning rats, induces a better human obesity model than very high-fat diet.

In the present study, we associated a high-fat diet (HF group: 45% kcal from lipids) or very high-fat (VHF group: 60% kcal from lipids) diet with a fructose drink (10% fructose) for hydration. Normal rat chow that received the control diet (content 16.3% kcal from lipid-AIN93G) and water. The treatments were introduced soon after weaning and were administered for 70 days. We aimed to compare HF and VHF groups and find which acts as a better model mimicking human obesity. Body mass gain, final body weight, adipocyte area in inguinal depots, visceral and subcutaneous adipose depots, serum triacylglycerol, and VLDL-c were all higher in the HF group, followed by the VHF group, compared to the C group. Only the HF group showed hyperinsulinemia and hyperleptinemia and higher total caloric intake, Lee index, HOMA2-IR, and total cholesterol. Serum TNF-α and IL-6 levels were lower in the HF and VHF groups than in the C group at the end for 70 days. In Summary, the HF (45%) diet administered with fructose induced a higher similarity of metabolic and hormonal alterations associated with human obesity. PRACTICAL APPLICATIONS: High intake of lipids with sugary drinks has been associated with obesity and its comorbidities. Although a diet with 45% or 60% of lipids is considered hyperlipidic, they are different in their effects on eating behavior and also probably from a metabolic point of view. Common sense is that the reduction in intake of lipids is favorable to health. Our study shows that this is not wholly true, and this information contributes to the guidelines for the treatment of obesity. In addition, the scientific literature on the subject has shown the most diverse results and also the use of experimental models with few similarities with human obesity. Our findings can contribute as a good model of obesity initiated during childhood to investigate possible using nutritional strategies, or the adoption of ergogenic nutritional resources in future studies, for example.

Acute and subacute oral toxicity assessment of dry encapsulated and non-encapsulated green coffee fruit extracts.

The coffee fruit is a high source of bioactive compounds such as phenolic acids and methylxanthines, comprising chlorogenic acids and caffeine, respectively. Extract from this matrix may be used as supplement or active ingredient of functional foods, energy drinks, cosmetics or drugs. Safety of caffeine- and chlorogenic acid-rich encapsulated and non-encapsulated hydroethanolic extracts from green coffee fruit (GCFE) was assessed by acute and subacute toxicity tests. In the acute test, oral single dosage until 1000 mg/kg per body weight (bw) did not show any adverse effect on both female and male mice according to the Hippocratic screening and clinical parameters for a period of 14 days. While the oral median lethal dose of non-encapsulated GCFE was 5000 mg/kg bw/day, that of encapsulated GCFE was not detectable likely due to the delayed release of caffeine and other compounds from GCFE. Non-encapsulated GCFE displayed a stimulating effect at a dose of 1000 mg/kg bw/day after 30 min of oral administration, but not after 60 min. Daily consumption of encapsulated GCFE for 30 days showed no adverse effect in male rats even at the highest dose. Extrapolating this value of no-observed-adverse-effect level (1000 mg/kg bw/day) to human consumption, a human equivalent dose of 189 mg/kg bw/day or 11.34 g/day could be estimated for encapsulated GCFE considering a 60 kg adult body weight.

The antioxidant system in the soleus muscle of growing rats is stimulated by the administration of a low-protein/high-carbohydrate diet.

The aim of this study was to evaluate the generation of reactive oxygen species (ROS) by xanthine oxidase (XO), the enzymatic antioxidant system and oxidative damage in soleus and extensor digitorum longus (EDL) muscles of growing rats fed a low-protein, high-carbohydrate (LPHC; 6% protein, 74% carbohydrate) diet for 15 days. The LPHC diet increased the total antioxidant capacity by 45% and the activities of glutathione peroxidase (GPx), glutathione reductase and catalase in the soleus muscles. There was an increase in the carbonylated proteins with no increase thiobarbituric acid reactive substances (TBARS), although the XO activity had increased 20%. In EDL muscles, the LPHC diet increased XO activity by 66% and the TBARS levels by 80%, and only GPx had its activity increased. These results suggest that the enzymatic antioxidant system of the soleus muscle has a better response to the increase of ROS production stimulated by LPHC diet.

Exercise-induced effects on UCP1 expression in classical brown adipose tissue: a systematic review.

Understanding the impact of regular exercise training on uncoupling protein 1 (UCP1) activity in classical brown adipose tissue (CBAT) is vital to our knowledge of whole-body thermogenic activity. The purpose of this systematic review was to evaluate the available experimental evidence on the effect of regular exercise training on UCP1 expression in CBAT. We performed a literature search using PubMed (1966-2016), Scopus, and EMBASE (1974-2016). Studies in any language that examined the effect of regular exercise training on UCP1 expression in CBAT, and not white adipose tissue (WAT), were eligible. Reviews, editorials, and conference proceedings were excluded. Nine studies fulfilled the set criteria. Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. The quality of reporting the results in the included studies was assessed using the 38-item checklist of the Animal Research Reporting of In Vivo Experiments (ARRIVE). Based on the evidence available and a comprehensive analysis of different confounding factors, we conclude that regular exercise training does not represent a major stimulus of UCP1 expression in CBAT. However, regular exercise training may induce adaptive responses to CBAT thermogenic activity in cases where: (i) animals consume a high-fat diet, (ii) exercise is combined with cold exposure, and (iii) animals show endogenously low UCP1 levels. Finally, it is important to note an inconsistency in the results from the analysed studies, which may be attributed to a number of confounding factors, increased risk of bias, as well as low quality of reporting the results.

Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health.

INTRODUCTION: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT. HYPOTHESIS: Recent evidence support a role of l-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. l-Menthol-induced BAT thermogenesis has been suggested to occur by a ß-adrenergic-independent mechanism, avoiding potential side-effects due to extensive ß-adrenergic stimulation mediated by available beta receptor agonists. l-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in l-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary l-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals. CONCLUSIONS: The putative impact of chronic l-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized l-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans.

Higher insulin sensitivity in EDL muscle of rats fed a low-protein, high-carbohydrate diet inhibits the caspase-3 and ubiquitin-proteasome proteolytic systems but does not increase protein synthesis.

Compared with the extensor digitorum longus (EDL) muscle of control rats (C), the EDL muscle of rats fed a low-protein, high-carbohydrate diet (LPHC) showed a 36% reduction in mass. Muscle mass is determined by the balance between protein synthesis and proteolysis; thus, the aim of this work was to evaluate the components involved in these processes. Compared with the muscle from C rats, the EDL muscle from LPHC diet-fed rats showed a reduction (34%) in the in vitro basal protein synthesis and a 22% reduction in the in vitro basal proteolysis suggesting that the reduction in the mass can be associated with a change in the rate of the two processes. Soon after euthanasia, in the EDL muscles of the rats fed the LPHC diet for 15days, the activity of caspase-3 and that of components of the ubiquitin-proteasome system (atrogin-1 content and chymotrypsin-like activity) were decreased. The phosphorylation of p70(S6K) and 4E-BP1, proteins involved in protein synthesis, was also decreased. We observed an increase in the insulin-stimulated protein content of p-Akt. Thus, the higher insulin sensitivity in the EDL muscle of LPHC rats seemed to contribute to the lower proteolysis in LPHC rats. However, even with the higher insulin sensitivity, the reduction in p-E4-BP1 and p70(S6K) indicates a reduction in protein synthesis, showing that factors other than insulin can have a greater effect on the control of protein synthesis.

Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: an in vivo mechanism study.

Context Ethnopharmacological studies have demonstrated that plants of the Combretum genus presented antidiabetic activity, including Combretum lanceolatum Pohl ex Eichler (Combretaceae). Objective This study investigated the hepatic mechanisms of action of C. lanceolatum flowers ethanol extract (ClEtOH) related to its antihyperglycaemic effect in streptozotocin-diabetic rats. Materials and methods Male Wistar rats were divided into normal (N) and diabetic control (DC) rats treated with vehicle (water); diabetic rats treated with 500 mg/kg metformin (DMet) or 500 mg/kg ClEtOH (DT500). After 21 d of treatment, hepatic glucose and urea production were investigated through in situ perfused liver with l-glutamine. Changes in the phosphoenolpyruvate carboxykinase (PEPCK) levels and in the activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-signalling intermediates were also investigated. Results Similar to DMet, DT500 rats showed a reduction in the rates of hepatic production of glucose (46%) and urea (22%) in comparison with DC. This reduction was accompanied by a reduction in the PEPCK levels in liver of DT500 (28%) and DMet (43%) when compared with DC. AMPK phosphorylation levels were higher in the liver of DT500 (17%) and DMet (16%) rats. The basal AKT phosphorylation levels were increased in liver of DT500 rats, without differences in the insulin-stimulated AKT phosphorylation and in the insulin receptor levels between DC and DT500 rats. Discussion and conclusion The antidiabetic activity of ClEtOH can be attributed, at least in part, to inhibition of hepatic gluconeogenesis, probably due to the activation of both AMPK and AKT effectors and reduction in the PEPCK levels.

A new dammarane saponin and other triterpenoids from Siolmatra brasiliensis and evaluation of the antidiabetic activity of its extract.

Context Siolmatra brasiliensis (Cogn.) Baill (Cucurbitaceae) is a climbing plant widely used for the treatment of diabetes mellitus symptoms. Objective This work evaluates the antidiabetic activity of an extract of S. brasiliensis in streptozotocin-diabetic rats and promotes the phytochemical investigation to isolate the major compounds of the same extract. Materials and methods Male Wistar rats were divided into normal (N) and diabetic rats (DC) treated with water; diabetic rats treated with 3U insulin (DI) or with 250 (DSb250) or 500 mg/kg (DSb500) of hydroalcoholic extract of the stalks of S. brasiliensis, via oral gavage, for 21 days. Physiological and biochemical parameters classically altered in diabetes were monitored. The triterpenoids were isolated from the ethyl acetate fraction under silica gel column chromatography and Sephadex-LH20 methods and their structures were determined by NMR, HR-ESI-MS and DC analysis. Results When compared with DC, DSb250 rats showed a reduction in the hyperglycemia (DC: 26.46 ± 0.69 versus DSb250: 19.67 ± 1.06 mmol/L) and glycosuria (DC: 43.02 ± 3.19 versus DSb250: 28.46 ± 2.14 mmol/24 h) and increase in hepatic glycogen (DC: 14.44 ± 1.26 versus DSb250: 22.08 ± 4.26 mg/g). Three known cucurbitacins were isolated from a hydroalcoholic extract of S. brasiliensis, i.e., cayaponosides A1, B4, D, and a new dammarane saponin 3-O-ß-d-gentiobiosyl-26-O-ß-d-glucopyranosyl-20-hydroxydammar-24-ene. The structures of these compounds were elucidated by spectral data analysis of the natural products and their acetyl derivatives. Discussion and conclusion The known cucurbitacins and/or the new identified saponin may be related with the antidiabetic activity of S. brasiliensis.

Acute and subchronic antihyperglycemic activities of Bowdichia virgilioides roots in non-diabetic and diabetic rats.

AIM: The present study was undertaken to evaluate the acute and subchronic antihyperglycemic effects of methanolic extract of Bowdichia virgilioides root bark of B. virgilioides in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The extract (100, 250 or 500 mg/kg) was orally administered to male Wistar diabetic (STZ, 42 mg/kg i.v.) and non-diabetic rats into two main protocols: (i) subchronic experiments, where animals were treated for 21 days with B. virgilioides extract and the following parameters were evaluated: Body weight, fluid and food intake (determined daily), urinary glucose and urea (every 3 days) and glycemia (every 5 days). At the end of the experimental period, skeletal muscles (extensor digitorum longus [EDL] and soleus), retroperitoneal and epididymal white adipose tissues were collected and weighed; liver samples were used for the determination of the lipid and glycogen contents; (ii) acute experiments, which evaluated the alterations on fasting and post-prandial glycemia and on glucose tolerance using the oral glucose tolerance test (OGTT). RESULTS: In subchronic experiments, the treatment with B. virgilioides extract did not change any parameter evaluated in diabetic and non-diabetic animals. On fasting and post-prandial glycemia, the extract treatment did not promote changes in the glycemia values in diabetic or non-diabetic animals. In OGTT, the treatment with 500 mg/kg B. virgilioides extract reduced the hyperglycemia peak after a glucose overload, when compared with non-treated diabetic animals, resulting in a lower area under curve. CONCLUSION: The results of our work indicate that B. virgilioides root extract promotes an acute antihyperglycemic effect in STZ-diabetic rats; this effect probably occurs through an inhibition of the intestinal glucose absorption. The continuity of the research is necessary to elucidate these possibilities.

Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation.

Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata. MATERIAL AND METHODS: The inner stem bark extract of Cedrela odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500 mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500 mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma. RESULTS: The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose of the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but reduced the triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity. CONCLUSIONS: Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases and glucose transporter inhibitors and antioxidant property.

Effects of the acute exposition to glyphosate-based herbicide on oxidative stress parameters and antioxidant responses in a hybrid Amazon fish surubim (Pseudoplatystoma sp).

The aim of this study was to investigate the effects of acute glyphosate (active ingredient) exposure on the oxidative stress biomarkers and antioxidant defenses of a hybrid surubim (Pseudoplatystoma sp). The fish were exposed to different herbicide concentrations for 96 h. The thiobarbituric acid-reactive substances (TBARS), protein carbonyls and antioxidant responses were verified. The 15 mg a.pL(-1) of herbicide resulted in the death of 50% of the fish after 96 h. An increase in liver and muscle TBARS levels was observed when fish were exposed to the herbicide. The protein carbonyl content was also increased in the liver (4.5mg a.pL(-1) concentration) and brain (2.25 mg a.pL(-1) concentration). The antioxidant activities decreased in the liver and brain after exposure to herbicide. Levels of ascorbic acid in the liver (2.25 mg a.pL(-1) and 4.5 mg a.pL(-1) concentrations) and brain (2.25 mg a.pL(-1) concentration) were increased post-treatment. Levels of total thiols were increased in the liver and brain (2.25 mg L(-1) and 7.5mg a.pL(-1), respectively). Glyphosate exposure, at the tested concentrations affects surubim health by promoting changes that can affect their survival in natural environment. Some parameters as TBARS and protein carbonyl could be early biomarkers for Roundup exposure in this fish species.

Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats.

OBJECTIVE: The aim of this study was to evaluate glucose uptake and the contribution of glucose to fatty acid (FA) synthesis and the glycerol-3-phosphate (G3P) of triacylglycerol synthesis by interscapular brown adipose tissue (IBAT) of low-protein, high-carbohydrate (LPHC) diet-fed rats. METHODS: LPHC (6% protein; 74% carbohydrate) or control (17% protein; 63% carbohydrate) diets were administered to rats (∼ 100 g) for 15 d. Total FA and G3P synthesis and the synthesis of FA and G3P from glucose were evaluated in vivo by (3)H2O and (14)C-glucose. Sympathetic neural contribution for FA synthesis was evaluated by comparing the synthesis in denervated (7 d before) IBAT with that of the contralateral innervated side. The insulin signaling and ß3 adrenergic receptor (ß3-AR) contents, as well as others, were determined by Western blot (Student's t test or analysis of variance; P ≤ 0.05). RESULTS: Total FA synthesis in IBAT was 133% higher in the LPHC group and was reduced 85% and 70% by denervation for the LPHC and control groups, respectively. Glucose uptake was 3.5-fold higher in the IBAT of LPHC rats than in that of the control rats, and the contribution of glucose to the total FA synthesis increased by 12% in control rats compared with 18% in LPHC rats. The LPHC diet increased the G3P generation from glucose by 270% and the insulin receptor content and the p-AKT insulin stimulation in IBAT by 120% and reduced the ß3-AR content by 50%. CONCLUSIONS: The LPHC diet stimulated glucose uptake, both the total rates and the rates derived from glucose-dependent FA and G3P synthesis, by increasing the insulin sensitivity and the sympathetic flux, despite a reduction in the ß3-AR content.

A low-protein, high-carbohydrate diet increases de novo fatty acid synthesis from glycerol and glycerokinase content in the liver of growing rats.

We had previously shown that adipose tissue increased in rats fed a low-protein, high-carbohydrate (LPHC) diet (6% protein, 74% carbohydrate) without a simultaneous increase in the de novo fatty acids (FA) synthesis. In addition, impairment in insulin signaling in adipose tissues was observed in these rats. For this study, we hypothesized that the insulin signaling pathway is preserved in the livers from these rats, which contributes to an increase in liver lipogenesis and, consequently, an increase in the weight of the adipose tissue. We also hypothesized that glycerol from triacylglycerol is an important substrate for FA synthesis. Our results showed that administration of the LPHC diet induced an increase in the in vivo rate of total FA synthesis (150%) as well as FA synthesis from glucose (270%) in the liver. There were also increased rates of [U-¹4C]glycerol incorporation into glyceride-FA (15-fold), accompanied by increased glycerokinase content (30%) compared with livers of rats fed the control diet. The LPHC diet did not change the glycerol-3-phosphate generation from either glucose or glyceroneogenesis. There was an increase in the insulin sensitivity in liver from LPHC-fed rats, as evidenced by increases in IR(ß) (35%) levels and serine/threonine protein kinase (AKT) levels (75%), and basal (95%) and insulin-stimulated AKT phosphorylation (105%) levels. The LPHC diet also induced an increase in the liver sterol regulatory element-binding protein-1c content (50%). In summary, these data confirmed the hypothesis that lipogenesis and insulin signaling are increased in the livers of LPHC-fed rats and that glycerol is important not only for FA esterification but also for FA synthesis.

Combretum lanceolatum flowers extract shows antidiabetic activity through activation of AMPK by quercetin

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500 mg/kg of metformin and diabetic treated with 250 or 500 mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500 mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500 mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50 µg/mL of ClEtOH, similarly to the incubation with metformin (50 µg/mL) or quercetin (10 µg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin.

A soyabean diet does not modify the activity of brown adipose tissue but alters the rate of lipolysis in the retroperitoneal white adipose tissue of male rats recovering from early-life malnutrition.

Nutritional recovery with a soyabean diet decreases body and fat weights when compared with a casein diet. We investigated whether the reduced adiposity observed in rats recovering from early-life malnutrition with a soyabean diet results from alterations in lipid metabolism in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein during pregnancy and lactation were maintained on 17 % casein (CC and LC groups), 17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The rats maintained on a soyabean diet had similar relative food intakes, but lower body and retroperitoneal WAT weights and a reduced lipid content in the retroperitoneal WAT. The insulin levels were lower in the recovered rats and were elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling protein 1 content in the BAT were decreased in the recovered rats. The thermogenic capacity of the BAT was not affected by the soyabean diet. The lipogenesis rate in the retroperitoneal WAT was similar in all of the groups except for the LL group, which had exacerbated lipogenesis. The enhancement of the lipolysis rate by isoproterenol was decreased in white adipocytes from the soyabean-recovered rats and was elevated in adipocytes from the soyabean-control rats. Thus, in animals maintained on a soyabean diet, the proportions of fat deposits are determined by the lipolysis rate, which differs depending on the previous nutritional status.