Synergistic Effects of Vitamin D and Exercise on Diabetes-induced Gonadotoxicity in Male Wistar Rats: Role of Xanthine Oxidase/Uric Acid and Nrf2/NfkB Signaling.

Type 2 Diabetes mellitus (T2DM) is one of the oldest known chronic diseases, characterized by elevated fasting blood sugar (FBS). T2DM is a metabolic disorder that can distort the activities of multiple physiological systems, including the reproductive system. Although different drugs have been designed for managing this disorder, these drugs have been reported to have negative side effects. Hence, this study was designed to explore the possible synergistic effect of vitamin D and exercise on T2DM-induced testicular dysfunction. Thirty-six male Wistar rats were randomized into six (6) groups: control, diabetes untreated, diabetes treated with 1000 IU/kg of vitamin D, diabetes treated with 5 min/day of physical exercise, diabetes treated with vitamin D and exercise, diabetes treated with 180 mg/kg of metformin. T2DM induction led to a significant increase in FBS, lactate, and lactate dehydrogenase, and was reversed by vitamin D supplementation and exercise. Also, vitamin D and exercise synergistically blunted T2DM-induced oxido-inflammatory response evidenced by a significant decrease in testicular malondialdehyde, interleukin 1ß, interleukin 6, and tumor necrosis factor alpha, and an increase in superoxide dismutase, catalase, glutathione peroxidase, and interleukin 10. These events were associated with a decrease in T2DM-induced increase in XO, UA, and Nf-κb and an increase in T2DM-induced decrease in Nrf2. Also, vitamin D and EX reversed the observed impairment in sperm quality and testicular histology following T2DM-induction. This study revealed the synergistic effect of vitamin D and exercise on T2DM-induced testicular dysfunction.

Targeting liver and adipose tissue in obese mice: Effects of a N-acylethanolamine mixture on insulin resistance and adipocyte reprogramming.

N-acylethanolamines (NAEs) are endogenous lipid-signalling molecules involved in inflammation and energy metabolism. The potential pharmacological effect of NAE association in managing inflammation-based metabolic disorders is unexplored. To date, targeting liver-adipose axis can be considered a therapeutic approach for the treatment of obesity and related dysfunctions. Here, we investigated the metabolic effect of OLALIAMID® (OLA), an olive oil-derived NAE mixture, in limiting liver and adipose tissue (AT) dysfunction of high-fat diet (HFD)-fed mice. OLA reduced body weight and fat mass in obese mice, decreasing insulin resistance (IR), as shown by homeostasis model assessment index, and leptin/adiponectin ratio, a marker of adipocyte dysfunction. OLA improved serum lipid and hepatic profile and the immune/inflammatory pattern of metainflammation. In liver of HFD mice, OLA treatment counteracted glucose and lipid dysmetabolism, restoring insulin signalling (phosphorylation of AKT and AMPK), and reducing mRNAs of key markers of fatty acid accumulation. Furthermore, OLA positively affected AT function deeply altered by HFD by reprogramming of genes involved in thermogenesis of interscapular brown AT (iBAT) and subcutaneous white AT (scWAT), and inducing the beigeing of scWAT. Notably, the NAE mixture reduced inflammation in iBAT and promoted M1-to-M2 macrophage shift in scWAT of obese mice. The tissue and systemic anti-inflammatory effects of OLA and the increased expression of glucose transporter 4 in scWAT contributed to the improvement of gluco-lipid toxicity and insulin sensitivity. In conclusion, we demonstrated that this olive oil-derived NAE mixture is a valid nutritional strategy to counteract IR and obesity acting on liver-AT crosstalk, restoring both hepatic and AT function and metabolism.

Acute Antiplatelet Effects of an Oleocanthal-Rich Olive Oil in Type II Diabetic Patients: A Postprandial Study.

Postprandial dysmetabolism is a common entity of type 2 diabetes mellitus (T2DM) and may act as a daily stressor of the already dysfunctional diabetic platelets. This study aims to investigate whether oleocanthal-rich olive oils (OO), incorporated into a carbohydrate-rich meal, can affect postprandial dysmetabolism and platelet aggregation. Oleocanthal is a cyclooxygenase inhibitor with putative antiplatelet properties. In this randomized, single-blinded, crossover study, ten T2DM patients consumed five isocaloric meals containing 120 g white bread combined with: (i) 39 g butter, (ii) 39 g butter and 400 mg ibuprofen, (iii) 40 mL OO (phenolic content < 10 mg/Kg), (iv) 40 mL OO with 250 mg/Kg oleocanthal and (v) 40 mL OO with 500 mg/Kg oleocanthal. Metabolic markers along with ex vivo ADP- and thrombin receptor-activating peptide (TRAP)-induced platelet aggregation were measured before and for 4 h after the meals. The glycemic and lipidemic response was similar between meals. However, a sustained (90-240 min) dose-dependent reduction in platelets' sensitivity to both ADP (50-100%) and TRAP (20-50%) was observed after the oleocanthal meals in comparison to OO or butter meals. The antiplatelet effect of the OO containing 500 mg/Kg oleocanthal was comparable to that of the ibuprofen meal. In conclusion, the consumption of meals containing oleocanthal-rich OO can reduce platelet activity during the postprandial period, irrespective of postprandial hyperglycemia and lipidemia.

Refined diet consumption increases neuroinflammatory signalling through bile acid dysmetabolism.

Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the 'microbiota-gut-brain axis', the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.

Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease.

Alzheimer disease (AD) is associated with multiple etiologies and pathological mechanisms, among which oxidative stress (OS) appears as a major determinant. Intriguingly, OS arises in various pathways regulating brain functions, and it seems to link different hypotheses and mechanisms of AD neuropathology with high fidelity. The brain is particularly vulnerable to oxidative damage, mainly because of its unique lipid composition, resulting in an amplified cascade of redox reactions that target several cellular components/functions ultimately leading to neurodegeneration. The present review highlights the "OS hypothesis of AD," including amyloid beta-peptide-associated mechanisms, the role of lipid and protein oxidation unraveled by redox proteomics, and the antioxidant strategies that have been investigated to modulate the progression of AD. Collected studies from our groups and others have contributed to unraveling the close relationships between perturbation of redox homeostasis in the brain and AD neuropathology by elucidating redox-regulated events potentially involved in both the pathogenesis and progression of AD. However, the complexity of AD pathological mechanisms requires an in-depth understanding of several major intracellular pathways affecting redox homeostasis and relevant for brain functions. This understanding is crucial to developing pharmacological strategies targeting OS-mediated toxicity that may potentially contribute to slow AD progression as well as improve the quality of life of persons with this severe dementing disorder.

Lactate Metabolism, Signaling, and Function in Brain Development, Synaptic Plasticity, Angiogenesis, and Neurodegenerative Diseases.

Neural tissue requires a great metabolic demand despite negligible intrinsic energy stores. As a result, the central nervous system (CNS) depends upon a continuous influx of metabolic substrates from the blood. Disruption of this process can lead to impairment of neurological functions, loss of consciousness, and coma within minutes. Intricate neurovascular networks permit both spatially and temporally appropriate metabolic substrate delivery. Lactate is the end product of anaerobic or aerobic glycolysis, converted from pyruvate by lactate dehydrogenase-5 (LDH-5). Although abundant in the brain, it was traditionally considered a byproduct or waste of glycolysis. However, recent evidence indicates lactate may be an important energy source as well as a metabolic signaling molecule for the brain and astrocytes-the most abundant glial cell-playing a crucial role in energy delivery, storage, production, and utilization. The astrocyte-neuron lactate-shuttle hypothesis states that lactate, once released into the extracellular space by astrocytes, can be up-taken and metabolized by neurons. This review focuses on this hypothesis, highlighting lactate's emerging role in the brain, with particular emphasis on its role during development, synaptic plasticity, angiogenesis, and disease.

Childhood and Adolescent Obesity with Somatic Indicators of Stress, Inflammation, and Dysmetabolism before and after Intervention: A Meta-Analysis.

There have been numerous attempts to establish a correlation between obesity and stress, inflammatory, and dysmetabolism biomarkers in children and adolescents. Here, we performed a meta-analysis of existing studies to shed light on the elusive correlations of childhood and adolescent obesity with physiological indicators of stress, inflammation, and metabolism before and after lifestyle interventions. Observational studies, meta-analyses, narrative and systematic reviews were excluded. From a total of 53 articles, 11 were selected according to specific criteria. The biomarkers examined were circulating glucose, insulin, HDL, LDL, triglycerides, adiponectin, leptin, CRP, TNF-alpha, interleukin (IL)-6, systolic and diastolic blood pressure, and HOMA-IR. All analyses were performed using IBM SPSS Statistics Version 28.0.1.0 (142). The current meta-analysis provides evidence of a beneficial effect of a lifestyle intervention and/or drugs in children and adolescents living with obesity or overweight, consistent with a significant reduction in body fat-but not in BMI or waist circumference-an increase in circulating adiponectin and/or a reduction in serum insulin levels and diastolic blood pressure, and a trend towards a reduction of circulating leptin and glucose levels, as well as of the HOMA-IR. This meta-analysis indicates that lifestyle interventions could reduce overweight-/obesity-associated systemic inflammation and dysmetabolism even without an apparent decrease in BMI.

Serum metabolomics profiling by proton nuclear magnetic resonance spectrometry of the response to single oral macronutrient challenges in women with polycystic ovary syndrome (PCOS) compared with male and female controls.

BACKGROUND: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the-art proton nuclear magnetic resonance spectrometry (1H-NMRS) metabolomics profiling, that androgen excess in women induces a certain masculinization of postprandial metabolism that is modulated by obesity. MATERIALS AND METHODS: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity. Patients were submitted to isocaloric separate glucose, lipid and protein oral challenges in alternate days and fasting and postprandial serum samples were submitted to 1H-NMRS metabolomics profiling for quantification of 36 low-molecular-weight polar metabolites. RESULTS: The largest postprandial changes were observed after glucose and protein intake, with lipid ingestion inducing smaller differences. Changes after glucose intake consisted of a marked increase in carbohydrates and byproducts of glycolysis, and an overall decrease in byproducts of proteolysis, lipolysis and ketogenesis. After the protein load, most amino acids and derivatives increased markedly, in parallel to an increase in pyruvate and a decrease in 3-hydroxybutyric acid and glycerol. Obesity increased ß- and D-glucose and pyruvate levels, with this effect being observed mostly after glucose ingestion in women with PCOS. Regardless of the type of macronutrient, men presented increased lysine and decreased 3-hydroxybutyric acid. In addition, non-obese men showed increased postprandial ß-glucose and decreased pyroglutamic acid, compared with non-obese control women. We observed a common pattern of postprandial changes in branched-chain and aromatic amino acids, where men showed greater amino acids increases after protein intake than control women and patients with PCOS but only within the non-obese participants. Conversely, this increase was blunted in obese men but not in obese women, who even presented a larger increase in some amino acids compared with their non-obese counterparts. Interestingly, regardless of the type of macronutrient, only obese women with PCOS showed increased leucine, lysine, phenylalanine and tryptophan levels compared with non-obese patients. CONCLUSIONS: Serum 1H-NMRS metabolomics profiling indicated sexual dimorphism in the responses to oral macronutrient challenges, which were apparently driven by the central role of postprandial insulin effects with obesity, and to a lesser extent PCOS, exerting modifying roles derived from insulin resistance. Hence, obesity impaired metabolic flexibility in young adults, yet sex and sex hormones also influenced the regulation of postprandial metabolism.

The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. PCOS is associated with diabetes, obesity and cardiometabolic disease. Mild excess of androgens (male hormones) characterize PCOS, and facilitate that body fat accumulates in the visceral abdominal area. Visceral fat promotes insulin resistance increasing the risk for diabetes and cardiometabolic disease, and further androgen excess. We here explored intermediate metabolism after the separate administration of either carbohydrates, fats or proteins, in young adult women with or without PCOS and in men, using state-of-the-art proton nuclear magnetic resonance metabolomics profiling. Results suggest that postprandial metabolomics profiles reflect mostly insulin actions, with changes derived from insulin resistance being more important with obesity but also being influenced by male sex and PCOS in women.

Risk Factor Interactions, Non-High-Density Lipoprotein Cholesterol to Apolipoprotein B Ratio, and Severity of Coronary Arteriosclerosis in South Asian Individuals: An Observational Cohort Study.

Background South Asian individuals are at higher risk for arteriosclerotic cardiovascular disease and diabetes. The factors associated with arteriosclerotic cardiovascular disease severity and their interactions are unknown. Methods and Results This is a retrospective cohort study of the first 1162 South Asian participants enrolled in the South Asian Heart Center's AIM to Prevent Program who completed noncontrast coronary computed tomography scans. Using machine-learning algorithms, we identified and modeled the interaction of predictor variables with coronary artery calcification (CAC) severity in South Asian individuals. Anthropometric, laboratory, demographic, and lifestyle predictor variables were analyzed using continuous boosted regression trees to model the relationship with and in between predictor variables and CAC. Participants with CAC were older, predominately men, had smoking history, had personal histories of diabetes, hypertension, and hypercholesterolemia, and had family histories of coronary artery disease. Insulin, body mass index, blood pressure, fasting blood sugar, hemoglobin A1c, and waist-to-height ratio were associated with CAC but not low-density lipoprotein cholesterol or lipoprotein (a). The arteriosclerotic cardiovascular disease score failed to classify individuals. Only age, body mass index, non-high-density lipoprotein cholesterol/apolipoprotein B ratio, smoking risk, fasting blood sugar, and diastolic blood pressure were predictive, explaining 30.3% of CAC severity. A non-high-density lipoprotein cholesterol/apolipoprotein B ratio of 1.4 or less markedly increased coronary calcification. Conclusions Our findings highlight factors associated with dysmetabolism and cholesterol-depleted non-high-density lipoprotein cholesterol particles with coronary arteriosclerosis, possibly explaining the dual epidemics of diabetes and arteriosclerotic cardiovascular disease in this population. Markers of glucose dysmetabolism and the non-high-density lipoprotein cholesterol to apolipoprotein B ratio should become the focus of assessment for cardiovascular risk in South Asian individuals, with prevention strategies directed at improving glucose metabolic health.

Unraveling the Crosstalk between Lipids and NADPH Oxidases in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of end-stage renal disease. Abnormal lipid metabolism and intrarenal accumulation of lipids have been shown to be strongly correlated with the development and progression of diabetic kidney disease (DKD). Cholesterol, phospholipids, triglycerides, fatty acids, and sphingolipids are among the lipids that are altered in DKD, and their renal accumulation has been linked to the pathogenesis of the disease. In addition, NADPH oxidase-induced production of reactive oxygen species (ROS) plays a critical role in the development of DKD. Several types of lipids have been found to be tightly linked to NADPH oxidase-induced ROS production. This review aims to explore the interplay between lipids and NADPH oxidases in order to provide new insights into the pathogenesis of DKD and identify more effective targeted therapies for the disease.

New Tiaoxin Recipe alleviates energy metabolism disorders in an APPswe/PS1DE9 mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a typical neurodegenerative disease with a complex etiology. Until now, there has been no effective treatment available for AD; however, improving energy dysmetabolism, the key pathological event in the early stage of AD, can effectively delay the progression of AD. OBJECTIVE: This paper aims to investigate the therapeutic effect and potential mechanism of the new Tiaoxin recipe on early AD. METHODS: APP/PS1 mice were divided into a model group, a new Tiaoxin recipe group, and a donepezil group, and C57/BL mice were used for the control group. Mouse cognitive and learning abilities were tested using the Morris water maze test and a new object-recognition experiment. The 42 amino acid form of amyloid ß peptide (Aß1-42) content was detected by enzyme-linked immunosorbent assay, the senile plaque area was detected by thioflavin S staining, and the senescence-associated ß-galactosidase (SA-ß-gal)-positive area was detected by chemical staining. Also, the adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+), and nicotinamide adenine dinucleotide hydride (NADH) contents were detected using a biochemical method, and the cluster of differentiation 38 (CD38) and silent mating-type information regulation 2 homolog 3 (SIRT3) protein expression levels were detected by immunofluorescence and Western blot analysis. RESULTS: Compared with those of the control group, the learning and memory abilities of the model group were impaired; the senile plaque deposition, Aß1-42 content, and SA-ßgal-positive staining area were increased; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were decreased; the CD38 protein expression level was increased; and the SIRT3 protein expression level was decreased. Following intervention with the new Tiaoxin recipe, the learning and memory abilities were improved; the senile plaque deposition, Aß1-42 content, and SA-ßgal-positive area were reduced; the ATP concentration, NAD+ concentration, and NAD+/NADH ratio were increased; CD38 protein expression was decreased, and SIRT3 protein expression was increased. CONCLUSION: This study shows that the new Tiaoxin Recipe can improve cognitive ability and reduce the Aß1-42 content and senile plaque deposition in APP/PS1 mice, which may occur through the downregulation of CD38 protein expression, upregulation of SIRT3 protein expression, restoration of the NAD+ level, promotion of ATP synthesis, mitigation of energy metabolism disorders.

A PCOS Paradox: Does Inositol Therapy Find a Rationale in All the Different Phenotypes?

A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected by an endocrine and metabolic issue. The term PCOS might not be appropriate to indicate the phenotypes described by the Rotterdam criteria, since the only phenotype with a gynecological issue alone is PCOS phenotype D. This novel perspective regarding how PCOS is currently defined leads the way to a reinterpretation of the entire pathological context and the treatment prescribed, such as inositols. A new point of view on the etiopathogenesis of the disease completely changes the current meaning of PCOS and consequently the therapeutic rationale evaluated to date.

Diabetes Mellitus and Energy Dysmetabolism in Alzheimer's Disease: Understanding the Relationships and Potential Therapeutic Targets.

Over the last century, there has been a gradual but sustained increase in life expectancy globally. A consequence of increased life expectancy is an associated rise in the prevalence of agerelated chronic debilitating neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and multiple sclerosis. These disorders, which are generally characterised by the loss of motor/sensory neurons and cognitive decline, have continued to confound researchers who are working tirelessly to define their pathogenetic mechanisms and develop effective therapies. In the last few years, there has been increasing evidence of the existence of a relationship between energy metabolism and neurodegeneration, with reports that type 2 diabetes mellitus increases the risk of AD. Evidence from preclinical and epidemiologic studies has associated dysmetabolism and dysmetabolic syndromes with the development of neurodegenerative changes. More recently, diabetes mellitus and energy dysmetabolism have been linked to the aetiopathogenesis of AD. Moreover, metabolic hormones, including ghrelin, leptin, insulin, and insulin-like growth factor (IGF)-1, have been reported to play key roles in the regulation of neuronal injury and loss in neurodegenerative diseases like AD. In this narrative review, we examine the current scientific evidence regarding the role of dysmetabolism (including diabetes mellitus and metabolic syndrome) in AD and how it impacts disease progression and the development of novel therapies in AD.

Perigestational exposure of a combination of a high-fat diet and pesticide impacts the metabolic and microbiotic status of dams and pups; a preventive strategy based on prebiotics.

PURPOSE: Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin. METHODS: From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues). RESULTS: HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure. CONCLUSION: Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases.

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.

Introduction: Frontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs. Methods: By the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer's disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects. Results: A statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers. Discussion: These results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis.

Overnutrition during Pregnancy and Lactation Induces Gender-Dependent Dysmetabolism in the Offspring Accompanied by Heightened Stress and Anxiety.

Maternal obesity and gestational diabetes predispose the next generation to metabolic disturbances. Moreover, the lactation phase also stands as a critical phase for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here, we investigate the consequences of a maternal lipid-rich diet during gestation and lactation and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that was fed a standard diet during the gestation and lactation periods and an overnutrition group that was fed a high-fat diet (HF, 60% lipid-rich) during the same phases. The offspring were analyzed at postnatal days 21 and 28 and at 2 months old (PD21, PD28, and PD60) for their metabolic profiles (weight, fasting glycemia insulin sensitivity, and glucose tolerance) and euthanized for brain collection to evaluate metabolism and inflammation in the hypothalamus, hippocampus, and prefrontal cortex using Western blot markers of synaptic dynamics. At 2 months old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observed that the female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuated with age. In the offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. The offspring of the HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, the offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to an HF diet during pregnancy and lactation induces dysmetabolism in the offspring and is accompanied by heightened stress and anxiety. There was sexual dimorphism in the metabolic traits but not behavioral phenotypes.

Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical from Opuntia ficus indica, L.: A Critical Review of Accumulated Evidence and Perspectives.

Phytochemicals from plant foods are considered essential to human health. Known for their role in the adaptation of plants to their environment, these compounds can induce adaptive responses in cells, many of which are directed at maintaining the redox tone. Indicaxanthin is a long-known betalain pigment found in the genus Opuntia of cactus pear and highly concentrated in the edible fruits of O. ficus indica, L. whose bioactivity has been overlooked until recently. This review summarizes studies conducted so far in vitro and in vivo, most of which have been performed in our laboratory. The chemical and physicochemical characteristics of Indicaxanthin are reflected in the molecule's reducing properties and antioxidant effects and help explain its ability to interact with membranes, modulate redox-regulated cellular pathways, and possibly bind to protein molecules. Measurement of bioavailability in volunteers has been key to exploring its bioactivity; amounts consistent with dietary intake, or plasma concentration after dietary consumption of cactus pear fruit, have been used in experimental setups mimicking physiological or pathophysiological conditions, in cells and in animals, finally suggesting pharmacological potential and relevance of Indicaxanthin as a nutraceutical. In reporting experimental results, this review also aimed to raise questions and seek insights for further basic research and health promotion applications.

Long-term use of Lacticaseibacillus paracasei N1115 from early life alleviates high-fat-diet-induced obesity and dysmetabolism in mice.

Obesity has become one of the most serious public health problems worldwide, and an increasing number of studies indicate that the gut microbiota can affect host metabolism. Therefore, the present study was conducted to evaluate whether long-term use of probiotics can alleviate host obesity and metabolism by altering gut microbiota. The high-fat diet (HFD) starting from weaned period led to higher levels of visceral fat and a significantly heavier liver in male mice. Moreover, HFD resulted in disorders of glucose and lipid metabolism, changes in insulin-resistance indices (IR), and an increase in serum insulin and leptin in mice. Of note, 15 weeks use of Lacticaseibacillus paracasei N1115 decreased visceral fat, liver weight, serum levels of insulin and leptin, and IR and alleviated lipid dysmetabolism. HFD resulted in a significant increase in the relative abundance of Bilophila, Lachnoclostridium, and Blautia and may decrease the faecal short-chain fatty acid (SCFA) levels in mice; in turn, treatment with the potential probiotic strain L. paracasei N1115 protected mice from these negative effects. HFD significant impaired the physiology of the host especially in male mice and dramatically changed the composition of host gut microbiota. However, the use of potential probiotic strain, such as L. paracasei N1115, may prevent these impairments due to HFD via effecting the host gut microbiota and SCFA.