Hypercaloric Diet Research Articles

Role of Callistemon citrinus Leaf Phytosomes Against Oxidative Stress and Inflammation in Rats Fed with a High-Fat-Fructose Diet.

Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body's organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents.

Curcumin Modulates the Differential Effects of Fructose and High-Fat Diet on Renal Damage, Inflammation, Fibrosis, and Lipid Metabolism.

Dyslipidemia and obesity hypercaloric diet-induced lead to kidney damage. We investigated the effect of curcumin on the expression of proteins related to inflammation, fibrosis, fatty acids metabolism, kidney damage, and morphological changes in the kidneys of mice hypercaloric diets-fed. Groups of 5-week-old C57BL/6 mice (n=6) were formed: Control (C), High-fructose diet (F), Highfructose diet and curcumin (F+Cur), High-fat diet (HFD), High-fat diet and curcumin (HFD+Cur), High-fat diet and fructose (HFD+F), High-fat diet, fructose and curcumin (HFD+F+Cur), treated for 16 weeks with 30% (w/v) fructose, 60% (w/w) fat and 0.75% (w/w) curcumin. Kidneys were obtained for histomorphological and Western Blot analysis. Curcumin prevented TNF-α overexpression in the F and HFD+F groups. VLCAD expression was higher in the F, HFD, and HFD+F groups. PPARγ expression was lower in the F+Cur, HFD+Cur, and HFD+F+Cur groups. Curcumin prevented overexpression of CPT1 and KIM1 in the HFD+F and HFD groups. Curcumin prevented morphological lesions, fibrosis, and lipid deposition that were hypercaloric diet-induced. Chronic consumption of hypercaloric diets causes inflammation, fibrosis, and lipid deposition in the kidney. It is suggested that curcumin prevents renal structural damage, limits tissue lipid deposition, and differentially modulates renal injury depending on diet composition in mice fed high-fat and/or high-fructose diets.

Spent brewer yeast glucan improves metabolic parameters and inflammatory markers reducing health risky changes imposed by the consumption of hypercaloric diet

β-glucans from yeasts are prebiotic health-promoting food ingredients able to boost immune response. An environmentally friendly source of yeast glucans is the spent brewer's yeast. This study investigated the effects of the administration of carboxymethyl glucan (CMG) (20 mg/kg, 12 weeks, orally), a derivative of the β-glucan from spent brewer's yeast, on food intake, weight gain, dyslipidemia, glucose intolerance, pro-inflammatory state, and hepatic steatosis of rats receiving a hypercaloric diet. The animals were divided into three groups: Normocaloric control (NCT); Hypercaloric diet and saline (HCT); and Hypercaloric diet and CMG (H-CMG). CMG administration could reduce rats' caloric value and food intake, reducing the index of adiposity (HCT:7.2±0.4% vs H-CMG:5.3±0.4% p < 0.05) and weight gain (HCT:111.1±3.8g vs H-CMG: 68.3±4.9g p < 0.05). Furthermore, it improved lipemic and glycemic profiles and lowered hepatic lipid accumulation. CMG decreased Monocyte Chemoattractant Protein (MCP)-1 (H-CT: 89.5±1.8 pg/mL vs H-CMG: 50.7±12.2 pg/mL p < 0.05), Interleukin (IL)-12 (H-CT: 206.0±14.0 pg/mL vs H-CMG:132.4±19.9 pg/mL, p < 0.05), and C-reactive protein (CRP) levels and increased IL-10 levels, decreasing the cardiovascular risk and pro-inflammatory state. Therefore, CMG has beneficial effects in preventing weight gain and, consequently, improves the metabolic profile in rats while consuming a hypercaloric diet. Findings indicate the spent brewer's yeast CMG can be a strategy to attenuate the risky metabolic changes related to the consumption of a hypercaloric diet.

Effects of Extended Treatment with Protium heptaphyllum Liposomes on Metabolic Parameters of Obese Rats.

Protium heptaphyllum (P. heptaphyllum), popularly known as "almacega" or "white pitch", is widely used in folk medicine due to its antioxidant, anti-inflammatory and healing properties, attributed to its richness in flavonoids and terpenes. Therefore, this study aimed to evaluate the effects of treatment for 28 days with liposomes containing P. heptaphyllum leaf extract in obese animals. Male Wistar rats, subjected to a hypercaloric diet for 8 weeks to induce obesity (hypercaloric chow and water enriched with 30% sucrose, ad libitum), were treated with the plant formulation (1 mg kg-1day-1, via gavage) for 28 days. The study investigated morphological, metabolic, redox state, immunological and histological parameters in adipose and liver tissue. Rats were divided into four groups: control (C), liposomes with extract (H), obese (O) and obese treated with liposomes containing extract (OH). The results indicated that the obese group (O) presented weight gain, hepatic steatosis and alterations in metabolic and inflammatory parameters. However, treatment with liposomes (OH) reduced glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine and the lipid profile. In adipose tissue, the OH group showed decreased superoxide dismutase (SOD) activity and increased glutathione S-transferase (GST) activity, in contrast to the effects observed in liver GST. In the analysis of thiobarbituric-acid-reactive substances (TBARS), it was possible to observe an increase in all groups in adipose tissue and in group O in liver tissue, in addition to a reduction in TBARS in group OH in the liver, indicating modulation of oxidative stress. The treatment also increased the concentration of IL-10 and IL-17 in the liver and decreased that of IL-6 in adipose tissue. After 28 days of treatment, these results point to the therapeutic potential of treatment with P. heptaphyllum, not necessarily only against obesity, but also an effect per se of the liposomes, possibly due to the high concentration of flavonoids present in the plant extract.

Associations between hypercaloric diet and caffeine intake and their implications on pregnancy outcomes in a murine model

Associations between hypercaloric diet and caffeine intake and their implications on pregnancy outcomes in a murine model

Jabuticaba (Myrciaria trunciflora) extract improves metabolic and behavioral markers of obese rats fed on a hypercaloric diet.

Obesity is a metabolic disease that affects many individuals around the world, related to imbalance between energy consumption and expenditure, which can lead to comorbidities. A healthy diet can significantly contribute to the prevention or treatment of this condition. Jabuticaba is an emerging fruit presenting a wide range of bioactive compounds and is being extensively studied due to its effects on lipid metabolism. The aim of this study was to evaluate the jabuticaba extract in the anxious-like behavior and in the lipid and oxidative metabolism in the context of obesity. Forty male Wistar rats divided into five groups were used. The animals received a standard diet and/or a hypercaloric diet and after 60 days of induction, interventions were carried out with jabuticaba extract (5% and 10%) via gavage for 30 days. It can be observed that the jabuticaba extract was able to reverse the anxious behavior observed in obese animals and modulate parameters of lipid and oxidative metabolism. We observed a reduction in cholesterol and triglyceride levels compared to obese animals. Furthermore, we observed an improvement in oxidative parameters, with a reduction in protein carbonylation in the liver and modulation of antioxidant enzymes such as superoxide dismutase and catalase. Contrary to expectations, we did not observe changes in leptin, adiponectin and tumor necrosis factor alpha (TNF-α) levels. Our work demonstrates that jabuticaba extract can improve metabolic, oxidative and behavioral changes in animals with obesity. © 2024 Society of Chemical Industry.

Whole tomato lipidic extract improved sperm quality in obese rats induced by a high-carbohydrate diet.

Obesity represents a risk in the development of metabolic and oxidative stress (OS), as well as in male infertility. There is still no pharmacological treatment for obesity-induced male infertility, but the use of natural antioxidants has been proposed as a treatment. The aim of this work is to evaluate the effect of a whole tomato lipid extract on rats that decreased their fertility and spermatogenesis after being induced obese with a high carbohydrate diet. One hundred fourteen male Wistar rats of 12weeks of age were used. Two groups were randomly formed non-obese control group (C, n=54) and obese group (Ob, n=54) that received 30% w/v sucrose solution for 3 months. Subsequently, the C and Ob group were divided into two groups: vehicle (C-Vh and Ob-Vh) that received corn oil as vehicle and tomato lipid extract (C-Ex and Ob-Ex) that received whole tomato lipid extract. The groups that received a hypercaloric diet had a gain in visceral and retroperitoneal adipose tissue, an increase in total cholesterol and triglyceride levels, increased OS in the testis, and lesions in testicular histology, as well as a reduction in testicular size and sperm quality parameters (motility, viability, and concentration). Treatment with whole tomato lipid extract significantly decreased the weight of gonadal adipose tissue and OS, maintained testicular size, showed a significant increase in sperm quality parameters and improved histology of seminiferous tubules. These results demonstrate a greater therapeutic and beneficial effect of the tomato lipid extract on sperm quality parameters in obese rats and therefore on fertility.

Influence of non-alcoholic fatty liver disease on reproductive function in an experiment

BACKGROUND: Currently, the attention of specialists is drawn to the relationship between non-alcoholic fatty liver disease and the development of reproductive disorders in both men and women. To better understand the etiology of these conditions and the mechanisms of pathogenesis, experimental models are being developed. A model using a hypercaloric diet containing increased amounts of carbohydrates is presented in this study. AIM: The aim of this study is to study the effect of non-alcoholic fatty liver disease on the reproductive function of female Wistar rats. MATERIALS AND METHODS: The study was conducted on 30 female Wistar rats, which were divided into two groups. The rats in the control group received standard nutrition. The non-alcoholic fatty liver disease model was reproduced in rats of the experimental group. To verify the diagnosis in the groups, changes in animal body weight, total cholesterol, triglycerides and glucose were assessed. After the diagnosis of non-alcoholic fatty liver disease was established, males were placed with the females to assess the females’ fertility. RESULTS: Keeping animals on a high-carbohydrate diet led to obesity in the females of the experimental group. In rats with non-alcoholic fatty liver disease, a significant increase in the blood levels of total cholesterol and triglycerides, as well as glucose, was found. A significant decrease in the number of pregnancies was recorded in the group with non-alcoholic fatty liver disease. A decrease in the number of individuals in the offspring was also revealed. CONCLUSIONS: The results of the experiment indicate that the use of a hypercaloric diet in rats causes the development of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease significantly reduces the fertility of female laboratory rats and reduces the number of individuals in the litter. This model can be used to study the causes of the development of the disease, as well as to better understand the mechanisms underlying reproductive dysfunction in patients.

Effect of Bidens tripartita leaf supplementation on the organism of rats fed a hypercaloric diet high in fat and fructose

Herbs play an important role in folk medicine, and scientific research has confirmed the properties of their use as an alternative treatment, including the treatment and mild correction of metabolic disorders during disease. Trifid bur-marigold (Bidens tripartita) is a pharmacopoeial herbal raw material that is widely used in clinical practice as an external remedy for skin lesions and as an internal remedy for digestive and respiratory disorders. In this work, the general effect of dried leaves of B. tripartita on physiological activity and metabolic processes in model animals on a high-calorie diet was determined. For the experiment, three groups of 18 male white laboratory rats were formed and fed a hypercaloric diet (increased fat content and 20% fructose solution instead of water) for 27 days, in addition to 0.4% and 4.0% dried leaves of B. tripartita. The consumption of 0.4% and 4.0% of the medicinal plant resulted in a significant delay in the body weight gain and the average daily weight gain of the rats compared to the control group. Dried leaves of B. tripartita in the diet of rats decreased the relative weight of the thymus and increased the relative weight of the brain, and at a dose of 4.0%, increased the relative weight of the lungs and individual large intestines (cecum and colon). Dietary supplementation with B. tripartita caused an increase in globulin concentration and changes in protein coefficient. Blood parameters such as: urea, urea nitrogen, inorganic phosphorus, glucose and bilirubin levels changed depending on the dose. In the general blood test, consumption of dried leaves of B. tripartita caused a decrease in hematocrit, hemoglobin concentration and platelet count, but increased the number of eosinophils. Bidens tripartita at both concentrations significantly increased ALT activity with a corresponding change in the blood De Ritis ratio. The addition of 20 g of B. tripartita leaves to the diet increased alkaline phosphatase activity and decreased alpha-amylase activity, while 200 g increased blood gamma-glutamyltransferase activity. At the end of the experiment, the rats' orientation activity, determined in the open field, changed according to the herb dose consumed: 0.4% leaves caused an increase and 4.0% a decrease. Physical activity was reduced and emotional state increased, regardless of the dose of dried B. tripartita leaves, compared to the control group of animals. The results obtained show that the addition of B. tripartita dried leaves as a dietary supplement to a high-calorie diet is safe, does not cause pathological changes or side effects, and has a significant effect on metabolic processes. This provides theoretical support for the use of B. tripartita dried leaves in the manufacture of nutraceutical and pharmacological products for the correction of metabolic disorders in humans and animals. The doses and duration of their application require further studies.

Effects of a Functional Food Made with Salvia hispanica L. (Chia Seed), Amaranthus hypochondriacus L. (Amaranth), and an Ethanolic Extract of Curcuma longa L. (Curcumin) in a Rat Model of Childhood Obesity.

Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels.

Efectos de la dieta alta en calorías y el ejercicio físico en el pez cebra (Danio rerio)

Zebrafish are becoming a valid model for investigating obesity and its associated disorders within a scientific context. The comprehension of the metabolic parameters linked to heightened body mass, adiposity, and energy expenditure stands as an indispensable endeavor in unraveling metabolic requisites among vertebrates. In this particular investigation, a cohort of 48 zebrafish specimens was scrutinized to determine the impact of physical exercise when subjected to a hypercaloric diet. The subjects were categorized into four distinct groups, each group respectively assigned to maintenance diets (GM, n=12, and GMex, n=12) or hypercaloric diets (GH, n=12, and GHex, n=12), with or without concurrent engagement in physical exercise. Applying a one-way ANOVA, with a significance level of P ≤ 0.05, the results revealed noteworthy findings. Among the GMex group, regarding body mass, a statistically significant variance was observed during the initial week (0.30g ± 0.10). This disparity demonstrated a reduction of 30.83% in the subsequent week, 33.59% in the fourth week, and 40.01% in the sixth week. Similarly, within the GH group, the analysis of variance unveiled significant deviations in body mass (in grams) from the inception of the study (0.32g ± 0.07), in comparison to measurements from the sixth through the thirteenth weeks. The GHex group exhibited significant differences in body mass between the first week (0.27g ± 0.08) and the subsequent weeks, extending until the thirteenth week. Furthermore, discernible variations in the length (in centimeters) of the zebrafish specimens were recorded, with statistical significance observed from the ninth (3.29cm ± 0.33) to the thirteenth weeks (3.61cm ± 0.33). The implementation of a hypercaloric diet yielded an augmentation in body mass. Additionally, the combination of this dietary regimen with physical exercise further contributed to an augmentation in the length of the zebrafish specimens. Collectively, the proposed model exhibited the capability to induce discernible metabolic effects, thereby enhancing our understanding of the intricate interplay between diet, exercise, and metabolic dynamics.

Sex and tissue-specific downregulation of miR410-3p in a mouse model of cardiometabolic diseases

The brain Renin-Angiotensin System (RAS) plays a pivotal role in controlling cardiometabolic homeostasis, fluid balance, and other functions including inflammation. Previous studies have shown that more than a thousand microRNA (miRNA) families regulate RAS genes expression, and their dysregulation has been associated with HTN, cardiac ischemia, and aging. Recently, we observed that hypercaloric diet (HCD) programming resulted in differentially expressed miRNA in the hypothalamus of only the male progeny, including miR-410-3p which is thought to target angiotensin-II type 1 receptors (AT1R). Here, we aimed to investigate whether miR-410-3p regulate AT1R expression in a mouse model of cardiometabolic disease (CMD) exhibiting hypertension, diabetes and obesity. C57BI/6J mice (3-week-old, both sexes, n=10) were fed a HCD (D12492. 60 kcal% Fat, Research Diets, USA) while weight and fasting blood glucose levels were measured weekly to ensure the acquisition of metabolic syndrome. At 12 weeks of age, the mice were infused subcutaneously (osmotic pump model 1004, Alzet) with Ang-II (600 ng/kg/min/4 weeks). Gene expression of miR-410-3p (QRT-PCR) was reduced in the hypothalamus of CMD male mice (0.5 ±0.1 vs.1.0 ±0.1, p&lt;0.05) but increased in females (1.6 ±0.4 vs.0.7 ±0.2, p&lt;0.001), while both sexes showed a reduction in the heart (Males: 0.2 ±0.0 vs.1.7 ±0.3; Females: 0.23 ±0.0 vs. 3.2 ±0.3, p&lt;0.01). AT1R protein expression (Capillary Western) was increased in the hypothalamus of CMD male (1.5 ±0.1 vs.1.0 ±0.2, p&lt;0.05) mice but not in females (1.0 ±0.1 vs.1.2 ±0.1, P&gt;0.05) while both sexes exhibited elevated levels in the heart (Males: 2.0 ±0.1 vs. 1.0 ±0.1; Females: 2.3 ±0.1 vs. 1.3 ±0.2, p&lt;0.05). Binding specificity (luciferase assay) was further assessed between miR-410-3p and the 3’UTR of AT1R. Binding was decreased in presence of miR410-3p mimic (0.9 ±0.0 vs. 2.1 ±0.0; p&lt;0.001) and enhanced by a miR410-3p inhibitor (2.5 ±0.1 vs. 2.1 ±0.0; p&lt;0.01), confirming that AT1R is a direct target of miR410-3p. Together, our data suggest that in CMD downregulation of miR410-3p is associated with the upregulation of AT1R both in the hypothalamus and heart, notably in males. This positions miR410-3p as a possible new therapeutic strategy to control RAS overactivity in CMD. This work was supported in part by a research grant from the National Institutes of Health (HL163588). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Upregulation of miR-361-3p Is Associated With Impaired AT2 Receptor Expression in Cardiometabolic Diseases

Cardiometabolic homeostasis has been shown to be regulated by the brain Renin-Angiotensin System (RAS), including via epigenetic mechanisms. MicroRNA (miRNA) regulation is one of the most common mechanisms controlling the expression of RAS genes and has previously been implicated in hypertension, cardiac ischemia, and aging. Recently, we observed that hypercaloric diet (HCD) programming resulted in differentially expressed miRNA in the hypothalamus of only the male progeny, including miR-361-3p which is thought to target angiotensin-II type 2 receptors (AT2R). Here, we aimed to investigate whether miR-361-3p regulate AT2R expression in a mouse model of cardiometabolic disease (CMD) exhibiting hypertension, diabetes and obesity. C57BI/6J mice (3-week-old, both sexes, n=10) were fed a HCD (D12492. 60 kcal% Fat, Research Diets, USA) while weight and fasting blood glucose levels were measured weekly to ensure the acquisition of metabolic syndrome. At 12 weeks of age, the mice were infused subcutaneously (osmotic pump model 1004, Alzet) with Ang-II (600 ng/kg/min/4 weeks). BP, food intake and glycemia were recorded weekly while intraperitoneal glucose (GTT), insulin (ITT) tolerance tests and body composition (EchoMRI) were assessed at the end of the study. Gene expression of miR-361-3p (QRT-PCR) was increased in the hypothalamus of CMD male mice (2.0 ±0.5 vs.1.2 ±0.2, p&lt;0.05) but not in females (2.7 ±0.8 vs.2.5 ±0.4, P&gt;0.05). However, both sexes showed an increase in the heart (Males: 2.0 ±0.5 vs.1.0 ±0.3; Females: 1.6 ±0.4 vs. 0.8 ±0.2, p&lt;0.05) which was associated with decreased AT2R cardiac expression (Capillary Western) in CMD male (0.9 ±0.0 vs.1.0 ±0.0, p&lt;0.05) and females (0.1 ±0.0 vs.0.6 ±0.1, p&lt;0.001). Together, our data suggest that in CMD, upregulation of miR-361-3p is associated with the decrease of AT2R in the heart, possibly contributing to impaired cardiac function in this model. This positions inhibitors of miR-361-3p as a possible new therapeutic strategy to control RAS overactivity in CMD. This work was supported in part by a research grant from the National Institutes of Health (HL163588). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Stronger vasoconstriction and weaker vasodilation in mesenteric arteries of Ossabaw than Göttingen minipigs before manifestation of metabolic syndrome

The metabolic syndrome predisposes and contributes to the development and progression of atherosclerosis. The minipig strain “Ossabaw” is characterized by a polygenic predisposition to develop metabolic syndrome and diffuse atherosclerosis in response to a hypercaloric atherogenic diet. The aim of this study was to investigate whether Ossabaw minipigs exhibit an altered vasomotor function even before they develop their diseased phenotype. Mesenteric arteries of adult Ossabaw (n=30) and Göttingen minipigs (n=40), a pig strain without genetic predisposition to a metabolic syndrome, were harvested postmortem, dissected, and mounted on a myograph for isometric force measurements. Maximal vasoconstriction to smooth muscle cell depolarization with potassium chloride (KClmax) was repeatedly induced (twice 0.6×10−1 mol/L and twice 1.2×10−1 mol/L). Cumulative concentration-response curves were determined in response to 1×10−9 -1×10−4 mol/L norepinephrine. Endothelium-dependent and -independent vasodilation were analyzed in response to carbachol and nitroprusside, respectively (1×10−9 - 1×10−4 mol/L, each) after pre-constriction by norepinephrine. The baseline diameter of mesenteric arteries from Ossabaw minipigs was smaller than that from Göttingen minipigs (329±20 vs. 435±11 μm), and mesenteric arteries of Ossabaw minipigs developed a higher baseline force of contraction than mesenteric arteries of Göttingen minipigs (6.2±0.7 vs. 3.6±0.3 mN). The maximal vasoconstrictor response to KCl was comparable between the minipig strains. Vasoconstriction in response to norepinephrine was more pronounced in Ossabaw than in Göttingen minipigs (143±9 vs. 108±6% KClmax). Endothelium-dependent vasodilation (46.4±5.5 vs. 16.0±3.0% of norepinephrine-induced preconstriction) and -independent vasodilation (36.7±4.9 vs. 2.3±0.6% of norepinephrine-induced preconstriction) were less pronounced in Ossabaw than in Göttingen minipigs. Neither the differences in baseline diameter nor in baseline developed force of contraction had any effect on the above data, as analyzed in retrospectively matched subsets of mesenteric arteries with a comparable baseline diameter or a comparable baseline developed force of contraction, respectively. Even before the development of metabolic syndrome, vasomotor function is shifted to more vasoconstriction and less vasodilation in Ossabaw minipigs, suggesting a genetic predisposition for the early development of vascular dysfunction. Thus, Ossabaw minipigs may be a suitable model to reflect the human situation of a heterogeneous, genetically determined primordial risk constellation for vascular dysfunction. This work was supported by the German Research Foundation [SFB 1116 B08 to G.H. and P.K.] and the European COST ACTION in CARDIOPROTECTION [CA16225 to G.H. and IG16225 to G.H. and P.K.]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Convolutional Neural Network Classifies Beat-to-Beat Arterial Pressure Spectrograms and Wavelet Transforms according to Age, Sex, and Metabolic State: Novel Frequencies for Cardiovascular Risk Appraisal

Hemodynamic homeostasis is under the control of multiple systems. Continuous blood pressure (BP) time series carry information relevant to the pathophysiological status of the cardiovascular system. Beside average BP, different measures of variability provide prognostic value for distinguishing between cardiovascular risk states. The latter are derived from time- and frequency- domain analysis of BP recordings and are limited by their capacity to provide cumulative risk appraisal among different risk groups. The prediabetic state is associated with cardiovascular risk which is often described to be age- and sex-specific. In this study, we sought to determine distinctive features of continuous arterial pressure (AP) time-series for risk appraisal in a pre-established prediabetic rat model. To overcome the shortcomings associated with conventional BP variability parameters, we trained a convolutional neural network (CNN) using spectrograms and scalograms generated from short-term Fourier- and Morlet wavelet- transforms of AP time series, respectively, from male and female prediabetic rats fed a mild hypercaloric diet for 12- or 24- weeks and their corresponding controls. The CNN consisted of 5 convolutional layers, separated by batch normalization, ReLU activation, and max pooling. The outcome of the fifth convolutional layer had 40% of the data dropped out and delivered to a fully-connected dense layer and then to a softmax function. The data was divided into 80% training, 10% validation, and 10% test sets. The model classified spectrograms and scalograms with test accuracy of 90%+ for the different binary and multi-class classification tasks. On backward propagation of model scores, different salient frequencies were identified as critical features for classification of AP time-series. The identified frequencies were much higher than those typically used in conventional power spectral density (PSD) analysis. Using 3-way ANOVA or principal component analysis for comparison and clustering of the different cardiovascular risk groups of age, sex, and metabolic disease, respectively, according to PSD at the identified peaks does not yield suffcient risk appraisal. This indicates that the CNN possibly captures non-linear relations which are undetectable using inherently linear methods.The results indicate sex- and age-specific patterns of cardiovascular deterioration in prediabetes. Use of artificial intelligence models for the identification of abnormal BP fluctuation patterns can provide suffcient risk appraisal needed for early intervention, particularly in at-risk patients lacking clinical signs of overt cardiovascular disease. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Activation of hepatic acetyl-CoA carboxylase by S-nitrosylation in response to diet

Nitric oxide (NO), produced primarily by nitric oxide synthase enzymes, is known to influence energy metabolism by stimulating fat uptake and oxidation. The effects of NO on de novo lipogenesis (DNL), however, are less clear. Here we demonstrate that hepatic expression of endothelial nitric oxide synthase is reduced following prolonged administration of a hypercaloric high-fat diet. This results in marked reduction in the amount of S-nitrosylation of liver proteins including notably acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in DNL. We further show that ACC S-nitrosylation markedly increases enzymatic activity. Diminished endothelial nitric oxide synthase expression and ACC S-nitrosylation may thus represent a physiological adaptation to caloric excess by constraining lipogenesis. Our findings demonstrate that S-nitrosylation of liver proteins is subject to dietary control and suggest that DNL is coupled to dietary and metabolic conditions through ACC S-nitrosylation.

The potential efficacy of Artemisia anuua L. extract nanoparticles in mitigating obesity-related-metabolic complications in hypercaloric diet-fed rats

ABSTRACT Obesity-related health problems are worsening in various societies worldwide. Artemisia anuua L. (AA) has distinctive health benefits, including anti-inflammatory, antioxidant, and insulin-sensitizing properties. Nanoformulation of herbal extracts is a new approach to enhance the bioavailability of natural products. This study aimed to evaluate the efficacy of AA extract, either the conventional extract (AAE) or its nano-form (AAEN), in modulating obesity-related metabolic complications in hypercaloric (high-fat/high-sucrose) diet-induced obese rats. Forty-eight rats were divided into two groups fed either a basal or hypercaloric diet for twelve weeks. Starting from the eighth week, each main group was subdivided into three subgroups and treated orally with either saline, AAE, or AAEN until the end of the experiment. Both AAE and AAEN exerted antiadipogenic effects. They reduced body weight and epididymal fat, mitigated dyslipidemia, improved glucose utilization and insulin resistance, reduced hyperleptinemia, increased serum adiponectin, and decreased oxidative stress and inflammatory markers. These results were mediated by regulating SIRT-1, PGC-1α, SREBP-1, PPAR-γ, FAS, LPL, IRS 1, and GLUT4 gene expression, suggesting an effect of AA on de novo lipogenesis and glucose utilization. The AAEN produced more expressive ameliorating effects than the conventional extract. AAE administration ameliorated the obesity-associated metabolic complications induced by feeding a hypercaloric diet, implying that this extract may be used as a complementary treatment option for obesity and its metabolic consequences. The antiadipogenic effectiveness of AAE was enhanced by its nanoformulation, suggesting that the nanoparticle system can be applied to boost other herbal medicine effectiveness.

Underlying Mechanisms behind the Brain-Gut-Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update.

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain-gut-liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain-gut-liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

Hypercaloric low-carbohydrate high-fat diet protects against the development of nonalcoholic fatty liver disease in obese mice in contrast to isocaloric Western diet.

Obesity and metabolic complications, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), are one of the greatest public health challenges of the 21st century. The major role of high sugar and carbohydrate consumption rather than caloric intake in obesity and NAFLD pathophysiology remains a subject of debate. A low-carbohydrate but high-fat diet (LCHFD) has shown promising results in obesity management, but its effects in preventing NAFLD need to be detailed. This study aims to compare the effects of a LCHFD with a high-fat high-sugar obesogenic Western diet (WD) on the progression of obesity, type 2 diabetes, and nonalcoholic fatty liver disease. Male C57BL/6J mice were initially fed a WD for 10 weeks. Subsequently, they were either switched to a LCHFD or maintained on the WD for an additional 6 weeks. Hepatic effects of the diet were explored by histological staining and RT-qPCR. After the initial 10 weeks WD feeding, LCHF diet demonstrated effectiveness in halting weight gain, maintaining a normal glucose tolerance and insulin levels, in comparison to the WD-fed mice, which developed obesity, glucose intolerance, increased insulin levels and induced NAFLD. In the liver, LCHFD mitigated the accumulation of hepatic triglycerides and the increase in Fasn relative gene expression compared to the WD mice. Beneficial effects of the LCHFD occurred despite a similar calorie intake compared to the WD mice. Our results emphasize the negative impact of a high sugar/carbohydrate and lipid association for obesity progression and NAFLD development. LCHFD has shown beneficial effects for NAFLD management, notably improving weight management, and maintaining a normal glucose tolerance and liver health.

Arthrospira platensis prevents contractile reactivity damage in obese rats fed a hypercaloric diet by positive modulating the Rho-A/Rho-kinase pathway, inflammation and oxidative stress

Obesity is characterized by excess fat, which favors the development of intestinal diseases. Arthrospira platensis (AP) has been the subject of several studies. However, few studies involve its effects on intestinal reactivity and associated mechanisms of action. The effects of AP and the mechanisms by which the seaweed prevents damage to contractile reactivity in the ileum were evaluated. Rats were fed on standard diet (SD), hypercaloric diet (HCD), or HCD supplemented with AP at a dose of 25 mg/kg (HCD + AP25). The preventive effects of seaweed were associated with positive modulation of the Rho kinase complex (ROCK), nitric oxide (NO), contractile prostanoids, superoxide dismutase (SOD) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling pathways, which may be associated with the presence of gamma linolenic acid (GLA), as the main component of AP. Therefore, AP appears as an adjunct in the prevention of obesity and intestinal diseases.