Diethylnitrosamine-Induced Liver Tumorigenesis in Mice Under High-Hat High-Sucrose Diet: Stepwise High-Resolution Ultrasound Imaging and Histopathological Correlations.

The hepatotoxic N-nitroso compound diethylnitrosamine (DEN) administered intraperitoneally (i.p.) induces liver neoplasms in rodents that reproducibly recapitulate some aspects of human hepatocarcinogenesis. In particular, DEN drives the stepwise formation of pre-neoplastic and neoplastic (benign or malignant) hepatocellular lesions reminiscent of the initiation-promotion-progression sequence typical of chemical carcinogenesis. In humans, the development of hepatocellular carcinoma (HCC) is also a multi-step process triggered by continuous hepatocellular injury, chronic inflammation, and compensatory hyperplasia that fuel the emergence of dysplastic liver lesions followed by the formation of early HCC. The DEN-induced liver tumorigenesis model represents a versatile preclinical tool that enables the study of many tumor development modifiers (genetic background, gene knockout or overexpression, diets, pollutants, or drugs) with a thorough follow-up of the multistage process on live animals by means of high-resolution imaging. Here, we provide a comprehensive protocol for the induction of hepatocellular neoplasms in wild-type C57BL/6J male mice following i.p. DEN injection (25 mg/kg) at 14 days of age and 36 weeks feeding of a high-fat high-sucrose (HFHS) diet. We emphasize the use of ultrasound liver imaging to follow tumor development and provide histopathological correlations. We also discuss the extrinsic and intrinsic factors known to modify the course of liver tumorigenesis in this model.

Signs of Glucagon Resistance After a 2-Week Hypercaloric Diet Intervention.

CONTEXT: Hyperglucagonemia is observed in individuals with obesity and contributes to the hyperglycemia of patients with type 2 diabetes. Hyperglucagonemia may develop due to steatosis-induced hepatic glucagon resistance resulting in impaired hepatic amino acid turnover and ensuing elevations of circulating glucagonotropic amino acids. OBJECTIVE: We evaluated whether glucagon resistance could be induced in healthy individuals by a hypercaloric diet intervention designed to increase hepatic fat content. METHODS: We recruited 20 healthy male individuals to follow a hypercaloric diet and a sedentary lifestyle for 2 weeks. Amino acid concentrations in response to infusion of glucagon were assessed during a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was assessed by magnetic resonance spectroscopy. RESULTS: The intervention led to increased hepatic fat content (382% [206%; 705%], P < .01). Glucagon infusion led to a decrease in the concentration of total amino acids on all experimental days, but the percentage change in total amino acids was reduced (-2.5% ± 0.5% vs -0.2% ± 0.7%, P = .015) and the average slope of the decline in the total amino acid concentration was less steep (-2.0 ± 1.2 vs -1.2 ± 0.3 µM/min, P = .016) after the intervention compared to baseline. The changes were normalized at follow-up. CONCLUSION: Our results indicate that short-term unhealthy behavior, which increases hepatic fat content, causes a reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals, which may explain the hyperglucagonemia associated with obesity and diabetes.

Effects of carnosine supplementation on markers for the pathophysiological development of metabolic dysfunction-associated steatotic liver disease in a diet-induced model.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

Effect of Low-Dose Progesterone on Glycemic Metabolism, Morphology and Function of Adipose Tissue and Pancreatic Islets in Diet-Induced Obese Female Mice.

BACKGROUND: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. METHODS: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. RESULTS: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. CONCLUSIONS: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.

Neonatal hyperoxia leads to white adipose tissue remodeling and susceptibility to hypercaloric diet.

Individuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well-established rodent model of preterm birth-related conditions in which newborn rats are exposed during postnatal days 3-10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high-fat high-fructose hypercaloric diet (HFFD). We evaluated 4-month-old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth-related conditions had long-lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long-term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue.

Chemical Characterization, Antilipidemic Effect and Anti-Obesity Activity of Ludwigia octovalvis in a Murine Model of Metabolic Syndrome.

Ludwigia octovalvis (Jacq.) P.H. Raven is widely used in traditional medicine for different illnesses, including diabetes and hypertension. However, its impact on lipotoxicity and metabolic syndrome in vivo has not been addressed. Therefore, the aim of this study was to evaluate the effects of this plant on the metabolic syndrome parameters in a C57BL6J mouse hypercaloric diet model. L. octovalvis hydroalcoholic extract and its ethyl acetate fraction (25 mg/kg/day) were used for sub-chronic assessment (10 weeks). Additionally, four subfractions (25 mg/kg) were evaluated in the postprandial triglyceridemia test in healthy C57BL6J mice. The hydroalcoholic extract and ethyl acetate fraction significantly decreased body weight gain (-6.9 g and -1.5 g), fasting glycemia (-46.1 and -31.2 mg/dL), systolic (-26.0 and -22.5 mmHg) and diastolic (-8.1 and 16.2 mmHg) blood pressure, free fatty acid concentration (-13.8 and -8.0 µg/mL) and insulin-resistance (measured by TyG index, -0.207 and -0.18), compared to the negative control. A postprandial triglyceridemia test showed that the effects in the sub-chronic model are due, at least in part, to improvement in this parameter. L. octovalvis treatments, particularly the hydroalcoholic extract, improve MS alterations and decrease free fatty acid concentration. These effects are possibly due to high contents of corilagin and ellagic acid.

Effects of different maternal diets on adipose tissue inflammation and liver tissue oxidative stress in dams and their female offspring.

Pregnancy and lactation are important stages of fetal development. Therefore, this study investigated how different maternal diets offered during gestation and lactation periods affect adipose tissue inflammation and liver tissue oxidative stress of dams and their female offspring. Female BALB/c albino mice (60 days old) were randomized into three groups receiving a standard (CONT), hypercaloric (HD), or restricted (RD) diet during the pregnancy. After birth, female offspring weaned at 21 days were divided into two groups that received a standard or restricted diet (CONT/CONT, CONT/RD, RD/CONT, RD/RD, HD/CONT, and HD/RD) until 100 days old. Histological, oxidative parameters and inflammatory infiltrate of dams' and offspring's liver and adipose tissue were evaluated. HD dams presented non-alcoholic steatohepatitis (NASH) diagnosis and an increase in tumor necrosis factor-alpha (TNF-α) concentrations when compared to the RD and CONT dams, indicating a pro-inflammatory state. High concentrations of malondialdehyde (MDA) formation and catalase (CAT) activity in HD when compared to the CONT in the liver. SOD activity decreased in RD mice compared to CONT, and the SOD/CAT ratio was decreased in the RD and HD in comparison to the CONT. The maternal diet leads to an increase in SOD in RD/RD compared to HD/RD. RD-fed dams showed an increase in inflammatory infiltrates compared to CONT, evidencing changes caused by a restrictive diet. In the HD/CONT offspring, we verified an increase in inflammatory infiltrates in relation to the offspring fed a standard diet. In conclusion, HD, and RD, during pregnancy and lactation, altered the liver and adipose tissues of mothers. Furthermore, the maternal diet negatively impacts the offspring's adipose tissue but does not cause liver damage in these animals in adult life.

Short-term Cafeteria Diet Is Associated with Fat Mass Accumulation, Systemic and Amygdala Inflammation, and Anxiety-like Behavior in Adult Male Wistar Rats.

Obesity is linked to metabolic, hormonal and biochemical alterations, and is also a risk factor for behavioral disorders. Evidence suggests that these disorders may be related to the consumption of hypercaloric diets, fat mass accumulation and changes in inflammation and redox status. Although much is known about the chronic effects of hypercaloric diets on mental health, few studies have evaluated the consequences of short-term exposure of these diets on behavior. The aim of this study was to evaluate nutritional, behavioral (anxiety-like), inflammatory and redox status parameters in adult male Wistar rats exposed to short-term cafeteria diet. Adult Wistar male rats (90 days-old; n = 12/group) received, during 14 days, the diets: Control- standard diet; Simple Cafeteria Diet (SCD)- homogeneous cafeteria diet. Varied Cafeteria Diet (VCD)- cafeteria diet with rotation and variation. Nutritional analyzes and tests for anxiety-like behaviors were performed, in addition to inflammatory and redox status measurements in blood and amygdala. The SCD group showed higher fat energy intake, while the VCD group consumed more energy from carbohydrates. SCD and VCD showed higher fat mass accumulation, in addition to higher levels of TNFα, INFγ, TBARS and FRAP in the blood. Also, SCD and VCD groups reported high levels of TNFα in the amygdala. Regarding behavioral evaluations, SCD and VCD groups showed anxiogenesis in the elevated plus maze, light-dark box, and open field tests. Therefore, the two cafeteria diets induced obesity and systemic inflammation, which in turn, resulted in an increase in amygdala TNFα levels and anxiety-like behaviors in Wistar rats.

Effect of Tecoma stans (L.) Juss. ex Kunth in a Murine Model of Metabolic Syndrome.

Metabolic syndrome is a constellation of abnormalities related to insulin resistance with an unfortunately high prevalence worldwide. Tecoma stans (L.) Juss. Ex Kunth. is a well-known medicinal plant that has been studied in several biological models related to diabetes mellitus. The aim of this study was to evaluate the effects of T. stans on a hypercaloric diet-induced metabolic syndrome model. An organic fraction obtained using liquid-liquid separation from the hydroalcoholic extract of T. stans and four subfractions of this organic fraction were administered for ten weeks to C57BL6J male mice previously fed with a hypercaloric diet. The hypercaloric diet caused changes in glucose levels (from 65.3 to 221.5 mg/dL), body weight (31.3 to 42.2 g), triglycerides (91.4 to 177.7 mg/dL), systolic (89.9 to 110.3 mmHg) and diastolic (61.6 to 73.7 mg/dL) blood pressure, and insulin resistance (4.47 to 5.16). Treatment with T. stans resulted in improvements in triglycerides (83.4-125.0 mg/dL), systolic blood pressure (75.1-91.8 mmHg), and insulin resistance (4.72-4.93). However, the organic fraction and hydroalcoholic extract produced a better response in diastolic blood pressure (52.8-56.4 mmHg). Luteolin, apigenin, and chrysoeriol were the major constituents in the most active subfractions. Treatment with T. stans, particularly a luteolin-rich organic fraction, achieved an improvement in metabolic syndrome alterations.

Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner.

Hypothalamic astrocytes are particularly affected by energy-dense food consumption. How the anatomical location of these glial cells and their spatial molecular distribution in the arcuate nucleus of the hypothalamus (ARC) determine the cellular response to a high caloric diet remains unclear. In this study, we investigated their distinctive molecular responses following exposure to a high-fat high-sugar (HFHS) diet, specifically in the ARC. Using RNA sequencing and proteomics, we showed that astrocytes have a distinct transcriptomic and proteomic profile dependent on their anatomical location, with a major proteomic reprogramming in hypothalamic astrocytes. By ARC single-cell sequencing, we observed that a HFHS diet dictates time- and cell- specific transcriptomic responses, revealing that astrocytes have the most distinct regulatory pattern compared to other cell types. Lastly, we topographically and molecularly characterized astrocytes expressing glial fibrillary acidic protein and/or aldehyde dehydrogenase 1 family member L1 in the ARC, of which the abundance was significantly increased, as well as the alteration in their spatial and molecular profiles, with a HFHS diet. Together, our results provide a detailed multi-omics view on the spatial and temporal changes of astrocytes particularly in the ARC during different time points of adaptation to a high calorie diet.

High-sugar/high-fat diet modulates the effects of chronic stress in cariocas high- and low-conditioned freezing rats.

Stress and eating disorders are closely related and are a topic of major concern due to their burden on human health. Engaging in unhealthy eating habits may come as a result of stress, and it often serves to alleviate the symptoms of anxiety or as a distraction from the stressor itself or self-awareness. However, it can also lead to negative feelings of a person's body figure, guilty, or shame. As diverse as these consequences are in humans, so are the effects of the combined administration of stress and hypercaloric food in animals' models. In this study, we assessed the influence of individual innate behavioral predisposition on the effects of chronic unpredictable mild stress and the dietary supplementation with high-sugar/high-fat food. These conditions were applied to male Carioca low- and high-conditioned freezing (CLF and CHF) rats for 21 days. Behavioral results show that the hypercaloric supplement had a protective effect over the alterations caused by the stress. Notably, it was more strongly observed in CHF rather than CLF animals. As the chronic stress led to an impaired behavior in the contextual fear conditioning and the forced swimming tests in the CLF line, animals fed with the HSHF pellet scored responses similar to their untreated control. On CHF rats, these effects also were seen to a broader extent on the open field test, where the locomotor behavior was also increased. No major effects of the diet were seen in the unstressed groups. Overall, our results show that the influences of both chronic stress and hypercaloric feeding depend on innate differences in fear response traits of male Carioca rats.

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring

Maternal diet is key to the progeny’s health since it may impact on the offspring’s adult life. In this study, mice dams received standard (CONT), restrictive (RD), or hypercaloric (HD) diets during mating, pregnancy, and lactation. Male offspring of each group of dams also received these diets: CONT, RD, HD. Aiming to evaluate the oxidative stress in the adipose tissue, reactive oxygen species (ROS) production, catalase (CAT), and superoxide dismutase (SOD) activities were analyzed in dams and offspring. In the adipose tissue and hypothalamus, gene expression of prolactin (Prlr) and estrogen alpha (Esr1) receptors was performed in dams and offspring. Protein expression of Stat5 was evaluated in the adipose tissue of the offspring from RD-fed dams. HD-fed dams increased triglycerides and leptin serum concentrations, and decreased SOD activity in the adipose tissue. In the offspring’s adipose tissue, we observed a maternal diet effect caused by HD, with increased ROS production and SOD and CAT activities. Gene expression of Prlr and Esr1 in the offspring’s adipose tissue was decreased due to maternal RD. Mice from HD-fed dams showed higher Stat5 expression compared to the offspring from CONT and RD dams in the adipose tissue. In the hypothalamus, we found decreased expression of Prlr in RD and HD dams, compared to CONT; and a maternal diet effect on Prlr and Esr1 gene expression in the offspring. In conclusion, we can affirm that maternal nutrition impacts the redox state and influences the gene expression of Prlr and Esr1, which are involved in energy metabolism, both peripherally and centrally in the adult life of the female offspring. (AU)

Dietary interventions in mice affect oxidative stress and gene expression of the Prlr and Esr1 in the adipose tissue and hypothalamus of dams and their offspring.

Maternal diet is key to the progeny's health since it may impact on the offspring's adult life. In this study, mice dams received standard (CONT), restrictive (RD), or hypercaloric (HD) diets during mating, pregnancy, and lactation. Male offspring of each group of dams also received these diets: CONT, RD, HD. Aiming to evaluate the oxidative stress in the adipose tissue, reactive oxygen species (ROS) production, catalase (CAT), and superoxide dismutase (SOD) activities were analyzed in dams and offspring. In the adipose tissue and hypothalamus, gene expression of prolactin (Prlr) and estrogen alpha (Esr1) receptors was performed in dams and offspring. Protein expression of Stat5 was evaluated in the adipose tissue of the offspring from RD-fed dams. HD-fed dams increased triglycerides and leptin serum concentrations, and decreased SOD activity in the adipose tissue. In the offspring's adipose tissue, we observed a maternal diet effect caused by HD, with increased ROS production and SOD and CAT activities. Gene expression of Prlr and Esr1 in the offspring's adipose tissue was decreased due to maternal RD. Mice from HD-fed dams showed higher Stat5 expression compared to the offspring from CONT and RD dams in the adipose tissue. In the hypothalamus, we found decreased expression of Prlr in RD and HD dams, compared to CONT; and a maternal diet effect on Prlr and Esr1 gene expression in the offspring. In conclusion, we can affirm that maternal nutrition impacts the redox state and influences the gene expression of Prlr and Esr1, which are involved in energy metabolism, both peripherally and centrally in the adult life of the female offspring.

The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus.

Introduction: Congenital hypothyroidism affects metabolic and thyroid programming, having a deleterious effect on bodyweight regulation promoting metabolic diseases. This work aimed to demonstrate the development of type 2 diabetes mellitus (T2D) in animals with congenital hypothyroidism, only by the consumption of a mild hypercaloric diet in the extrauterine stage. Methods: Two groups of female Wistar rats (n = 9): euthyroid and hypothyroid were used. Hypothyroidism was induced by a thyroidectomy with parathyroid reimplantation. Male offsprings post-weaning were divided into four groups (n = 10): euthyroid, hypothyroid, euthyroid + hypercaloric diet, and hypothyroid + hypercaloric diet. The hypercaloric diet consisted of ground commercial feed plus 20% lard and was administered until postnatal week 40. Bodyweight and energy intake were monitored weekly. Also, metabolic and hormonal markers related to cardiovascular risk, insulin resistance, and glucose tolerance were analyzed at week 40. Then, animals were sacrificed to perform the morphometric analysis of the pancreas and adipose tissue. Results: T2D was developed in animals fed a hypercaloric diet denoted by the presence of central obesity, hyperphagia, hyperglycemia, dyslipidemia, glucose tolerance, insulin resistance and hypertension, as well as changes in the cytoarchitecture of the pancreas and adipose tissue related to T2D. The results show that congenital hypothyroid animals had an increase in metabolic markers and an elevated cardiovascular risk. Conclusions: Congenital hypothyroid animals develop T2D, having the highest metabolic disturbances and a worsened clinical prognosis than euthyroid animals.

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics.

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

The Effects of Chronic Consumption of Lipid-Rich and Delipidated Bovine Dairy Milk on Brown Adipose Tissue Volume in Wild-Type Mice.

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. The ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of the MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high-fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, their body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in the BAT volume and mice consuming an HF diet in conjunction with FC BDM had a significantly greater BAT volume than all the other groups. Conversely, mice consuming an HF diet in addition to skim milk had a lower BAT volume compared to the HF control. The data presented suggest that the consumption of a high calorie diet in conjunction with FC BDM increases the BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors, including diet.

Effects of supplementation with kombucha and green banana flour on Wistar rats fed with a cafeteria diet.

INTRODUCTION: With the increase of chronic diseases as a consequence of the population's eating habits, there is also a growing interest in foods rich in bioactive compounds capable of mitigating these diseases. Thus, this study aimed to evaluate the effects of supplementation with kombucha and green banana flour (GBF) on Wistar rats fed with cafeteria diet (CAF). METHODS: The animals were randomized into five groups of seven animals each, which were fed with the following diets: Treatment 1 (T1): Control treatment/commercial feed; Treatment 2 (T2): cafeteria diet (CAF); Treatment 3 (T3): CAF + kombucha; Treatment 4 (T4): CAF + green banana flour (GBF); Treatment 5 (T5): CAF + GBF + kombucha. Daily weight gain, daily food consumption, feed conversion, blood glucose, total cholesterol and fractions, triglycerides, liver enzymes, antioxidant activity, and body composition were evaluated. RESULTS: T5 presented lower feed intake and less weight gain. Liver histology revealed vacuolization in all treatments except T1, which was confirmed by the results of liver enzymes. There was no increase in blood glucose, and changes were observed in the lipid profile of the animals. T1 had the lowest body fat and the highest protein levels. Differences were observed for the antioxidant capacity in the liver of animals among treatments. CONCLUSION: The intake of cafeteria diet altered the lipid and liver profile of the animals and the consumption of kombucha and GBF did not prevent these changes. The high polyphenols level of kombucha did not exert a hepatoprotective effect as an antioxidant. However, this supplementation generated greater satiety in the animals, leading to less weight gain until the end of the experiment.

Changes in metabolic and physiological biomarkers in Mangalarga Marchador horses with induced obesity.

This study aimed to characterize and correlate physiological and metabolic changes in horses fed a hypercaloric diet (HD). Nine mature horses with a mean initial body condition score of 2.9 ± 1 (scale, 1-9) were fed a high-calorie diet for 5 months. Fasting blood samples were collected before the study and biweekly for the duration of the project to determine the concentrations of cholesterol (CHOL), very low (VLDL), low (LDL) and high-density (HDL) lipoproteins, triglycerides, non-esterified fatty acids, and fructosamine. A low-dose oral glucose tolerance test (LGTT) was conducted before, 75 and 150 days after HD introduction. Mean arterial blood pressure was measured monthly. Following HD introduction, CHOL, LDL, HDL, and fructosamine blood concentrations increased (P < 0.001). These four variables were also positively and significantly correlated with the blood insulin response to LGTT. These findings confirm the occurrence of hypercholesterolemia concomitantly with insulin dysregulation development in horses exposed to HD.

Kidney Adaptations Prevent Loss of Trace Elements in Wistar Rats with Early Metabolic Syndrome.

Metabolic syndrome (MetS) represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance. These metabolic derangements present significant risk factors for chronic kidney disease that carries to loss of essential micronutrients, which accelerates comorbidity apparition. The work aimed was to evaluate the trace element homeostasis regarding morphological adaptations and renal function in MetS early-onset. Fifty male Wistar rats were divided into two groups: (a) control group and (b) hypercaloric diet group that developed MetS early-onset after 3 months. Classical zoometric parameters do not show changes; however, biochemical modifications were observed such as hyperglycemia, protein glycation, insulin resistance, dyslipidemia, hyperinsulinemia, and hypoadiponectinemia. MetS early-onset group observed renal structural modifications, but no functional changes. The structural modifications observed were minimal glomerular injury, glomerular basement membrane thickening, as well as mesangial and tubular cells that showed growth and proliferation. In serum and kidney (cortex and medulla), the concentrations of Zn, Fe, Cr, Mg, Mn, Cu, Co, and Ni were no differences between the experimental groups, but excretory fractions of these were lower in the hypercaloric diet group. In conclusion, MetS early-onset coexist renal structural modification and a hyperreabsorptive activity of essential trace elements that avoid its loss; thus, the excretory fraction of oligo-elements could be used a biomarker of early renal injury caused by metabolic diseases in the clinical practice.

Early life exposure to hypercaloric diet impairs eating behavior during weaning: The role of BDNF signaling and astrocyte marks.

Literature shows that gestational and/or lactational exposure to hypercaloric diets induces long term effects on eating behavior and the involvement of neurochemical mechanisms. We hypothesized that the effects of hypercaloric diets in early development phases can precede an overweight or an obesity status. The aim of the present study was to evaluate the impact of gestational and lactational exposure to cafeteria diet on eating behavior and neurochemical parameters, BDNF signaling, epigenetic and astrocyte marks in the hippocampus and olfactory bulb during the weaning phase. Pregnant female rats were randomized between standard and cafeteria diet, the respective diet was maintained through the lactational period. The framework of feeding pattern, meal, and its microstructure, was observed in postnatal day 20. Exposure to cafeteria diet increased the number of meals, associated with a lower first inter-meal interval and higher consumption in both genders, without any changes in body weight. Diet exposure also reduced the number of grooming, a behavior typically found at the end of meals. Hypercaloric diet exposure reduced BDNF levels in the olfactory bulb and hippocampus from rats of both sexes and increased the content of the TrkB receptor in hippocampi. It was observed an increase in HDAC5 levels, an epigenetic mark. Still, early exposure to the hypercaloric diet reduced hippocampal GFAP and PPARγ levels, without any effect on NeuN content, indicating that alterations in astrocytes can precede those neuronal outcomes. Our results showed that changes in interrelated neurochemical signaling, BDNF, and astrocyte marks, induced by hypercaloric diet in early stages of development may be related to impairment in the temporal distribution of eating pattern and consequent amounts of consumed food during the weaning phase.