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.

Impact of dietary vitamin A deficiency on body physiology and liver metabolism of Wistar rats.

Background: Studies suggest that vitamin A deficiency (VAD) can cause night blindness or xerophthalmia, hepatic and metabolic changes in the blood. Aim: Therefore, this work aimed to stablish a model of hypovitaminosis A in rats and to evaluate the effects of vitamin A deficiency on metabolic and oxidative parameters in the liver of rats. Methods: Male (n = 19), Wistar, rats (21-day-old) weighing 50g, divided into two experimental groups: Control Group (C), received AIN 93G diet and Vitamin A Deficiency Group (VAD), received AIN 93G vitamin A-free diet for 45 days. In this work, the parameters analyzed were: body mass, food and water intake, biochemical aspects in the blood, lipids and glycogen content, lipid peroxidation, carbonyl proteins and catalase activity in the liver. Results: In the VAD group, final body mass (9%), liver mass (28%), glycemia (14%), Total -cholesterol (17%), HDL -cholesterol (31%) and VLDL -cholesterol (30%) showed reduced (p < 0.05). The liver lipid (64%) and glyceride-fatty acid (74%) contents were higher in the VAD group. The carbonyl proteins in liver were increased by 171% (p < 0.05). Conclusion: In summary, these results suggest that the absence of vitamin A from the diet was effective in inducing characteristics of hypovitaminosis A in rats. This way, can be used for studies related to glucose and lipid metabolism.

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.

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.

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.

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.