Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Sex-Related Glycemic and Cardiovascular Responses After Continuous and Interval Aerobic Sessions in Patients With Type 1 Diabetes: A Randomized Crossover Study.

We aimed to investigate sex-related glycemic and cardiovascular responses after intensity- (moderate) and duration- (30 minutes) matched interval aerobic exercise (IAE) and continuous (CAE) aerobic exercise sessions in patients with type 1 diabetes mellitus (T1DM). A total of 19 volunteers (10 women) participated in 2 randomized and crossover sessions (1:1). Heart rate, systolic and diastolic blood pressure, double product, and blood glucose (BG) levels were measured before (PRE), immediately after (POST-0), and 20 minutes after (POST-20) each session. The rates of perceived exertion (RPE) and enjoyment levels (ELs) were assessed after each session. Generalized estimating equations were used to analyze the data (condition × time × sex). Regarding sex-related changes, men showed BG reductions at POST-0 and POST-20 after CAE (∆: -3.7 and -3.7 mmol/L, respectively) and only at POST-0 after IAE (∆: -1.6 mmol/L), with 1 episode of hypoglycemia occurring in the latter group. In contrast, women showed reduced BG values only after CAE at both time points (∆: -1.4 and -1.7 mmol/L) compared with PRE values. The decrease in BG levels at both time points was higher for men after CAE than IAE. Cardiovascular responses, RPEs, and ELs were similar between exercise sessions, except for blood pressure, which showed higher values in men. In conclusion, lower BG levels were observed after CAE, with greater reductions in men. Similar cardiovascular, RPE, and EL responses were found across sexes and sessions. Consideration of sex-specific recommendations may be warranted when prescribing aerobic exercise, particularly, for men with irregular physical activity levels.

The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.

AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.

Age-related differences in fluctuations in insulin resistance evaluated with HOMA-IR and triglyceride and glucose-based indices during the menstrual cycle, as determined using the NHANES cross-sectional dataset.

OBJECTIVES: To determine how age affects insulin resistance during the menstrual cycle and insulin resistance-associated indices: the Triglyceride-glucose and Triglyceride-glucose-BMI indexes. METHODS: This prospective observational study used fasting plasma glucose, fasting insulin, triglycerides, body mass index (BMI), and days since the start of the menstrual period collected from the NHANES dataset (1999-2006). Insulin resistance was determined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The participants were categorized as young (16-34 years) or older (>35 years). Rhythmicity during the menstrual cycle was analyzed using the Cosinor and Cosinor2 packages for R. MAIN OUTCOME MEASURES: Cosine fit curves for insulin resistance during the menstrual cycle and age-associated effects on rhythmicity. RESULTS: Using 1256 participants, rhythmicity was observed for fasting insulin and HOMA-IR (p < 0.05) but not for fasting plasma glucose, the Triglyceride-glucose index, or the Triglyceride-glucose-BMI index. Significant amplitudes for fasting insulin and HOMA-IR were observed when age was considered. Acrophases for fasting insulin and HOMA-IR were significant only for the younger group, and the differences between these groups were significant, suggesting that the changes in scores for insulin resistance for the younger and older groups occur at different times of their menstrual cycle. CONCLUSIONS: Insulin resistance does fluctuate during the menstrual cycle, and it is at a maximum at different times for younger and older women. Since these results are unadjusted, this study is preliminary and further investigation is required.

Analytical performance of publicly dispensed glucometers in primary health care in a southern Brazilian city.

Aims: This study aimed to assess the use of glucometers by patients and the analytical performance of glucometers provided by the primary care services. Methods: The analytical performance of 48 glucometers Accu-Chek® Active, was assessed through quintuplicate analyses of one Roche and one PNCQ (National Quality Control Program) control sample at different concentrations; 31 were also evaluated by a single proficiency testing sample. The evaluation metrics included imprecision, bias, and total error and were measured according to quality specifications based on biological variation (QSBV). Glucometer users answered a questionnaire regarding their experience. Results: Among the 48 glucometers evaluated with internal control samples, 17 met precision criteria at both control levels according to QSBV, while 24 met the criteria at only one control level. Of the 31 glucometers further evaluated through proficiency test, 11 met accuracy criteria according to QSBV, and only one device showed an unacceptable result. Out of these 31, only 15 demonstrated a total error within the acceptable maximum limits based on QSBV. Conclusions: Overall, our findings showed that patients had a good understanding of glucometer usage and suggested that some glucometers should be replaced, as they sometimes failed to meet even the manufacturer's acceptable variation limits, and/or did not meet QSBV.

Exploring the association of serum prolactin with serum glucose levels and clinical findings in a cohort of patients with early rheumatoid arthritis.

BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.

Targeting the immunoproteasome in hypothalamic neurons as a novel therapeutic strategy for high-fat diet-induced obesity and metabolic dysregulation.

OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.

Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.

ß-D-Glucose-Reduced Silver Nanoparticles Remodel the Tumor Microenvironment in a Murine Model of Triple-Negative Breast Cancer.

Breast cancer is the most diagnosed type of cancer worldwide and the second cause of death in women. Triple-negative breast cancer (TNBC) is the most aggressive, and due to the lack of specific targets, it is considered the most challenging subtype to treat and the subtype with the worst prognosis. The present study aims to determine the antitumor effect of beta-D-glucose-reduced silver nanoparticles (AgNPs-G) in a murine model of TNBC, as well as to study its effect on the tumor microenvironment. In an airbag model with 4T1 tumor cell implantation, the administration of AgNPs-G or doxorubicin showed antitumoral activity. Using immunohistochemistry it was demonstrated that treatment with AgNPs-G decreased the expression of PCNA, IDO, and GAL-3 and increased the expression of Caspase-3. In the tumor microenvironment, the treatment increased the percentage of memory T cells and innate effector cells and decreased CD4+ cells and regulatory T cells. There was also an increase in the levels of TNF-α, IFN-γ, and IL-6, while TNF-α was increased in serum. In conclusion, we suggest that AgNPs-G treatment has an antitumor effect that is demonstrated by its ability to remodel the tumor microenvironment in mice with TNBC.

High triglyceride-glucose index and HOMA-IR are associated with different cardiometabolic profile in adults from the ELSA-Brasil study.

BACKGROUND AND AIMS: Insulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS AND RESULTS: A cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35-74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson's r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Cohens kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations. CONCLUSION: TyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR.

GHSR signalling in perinatal phases is involved in liver metabolism at puberty.

Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2[1-14]. For this, two experimental models were used: (i) LEAP2[1-14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2[1-14] or MK677. Perinatal GHSR modulation by LEAP2[1-14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

Auditory enrichment with different genres of music for colony queens.

The aim was to determine changes in clinical parameters, glucose concentration, cortisol and behavior in colony queens in no music conditions compared with exposing to different genres of music. Mixed breed clinically healthy queens (N = 9) were used. Queens were studied under no music conditions (control=CON) and auditory enrichment: Soft Rock (M1), Motown (M2), Pop (M3), Frenchcore (M4) and music that was composed to be species-appropriate for cats (M5). The queens underwent auditory enrichment, including three days of silence (D1-3), five consecutive days of auditory enrichment (D4-8) and three days of silence (D9-11). We recorded clinical parameters, glucose, cortisol and behavior. Data were analyzed with GLIMMIX. Queens showed a significant increase of femoral pulse during exposure to M1, M2 and M4; and respiratory rate during exposure to M1, M2, M3 and M4 compared with CON. There was a significant increase in glucose during exposure to M2 and M5 compared with CON. However, there was a significant decrease in glucose during exposure to M4 compared with CON. There was a significant decrease in cortisol during exposure to M2 and M5 compared with CON. When we evaluated the ethogram, we observed a significant decrease in the percentage of interaction with other cats in M1 and M2 compared with CON. In addition, we found a significant decrease in the purring in M1 and M3 compared with CON. Auditory enrichment can be beneficial in situations that cause discomfort and distress in colony cats, such as in feline hospitalization; however, it should be acknowledged that there are limits to direct extrapolation.

Effects of acute consumption of a beverage based on extruded whole-grain pearl millet flour on glycemic and insulinemic control, food intake, and appetite sensation in eutrophic adults: A randomized cross-over clinical trial.

OBJECTIVES: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults. METHODS: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session. RESULTS: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage. CONCLUSIONS: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects.

Sodium-glucose cotransporter-2 inhibitors protect tissues via cellular and mitochondrial pathways: Experimental and clinical evidence.

Mitochondrial dysfunction is a key driver of cardiovascular disease (CVD) in metabolic syndrome and diabetes. This dysfunction promotes the production of reactive oxygen species (ROS), which cause oxidative stress and inflammation. Angiotensin II, the main mediator of the renin-angiotensin-aldosterone system, also contributes to CVD by promoting ROS production. Reduced activity of sirtuins (SIRTs), a family of proteins that regulate cellular metabolism, also worsens oxidative stress. Reduction of energy production by mitochondria is a common feature of all metabolic disorders. High SIRT levels and 5' adenosine monophosphate-activated protein kinase signaling stimulate hypoxia-inducible factor 1 beta, which promotes ketosis. Ketosis, in turn, increases autophagy and mitophagy, processes that clear cells of debris and protect against damage. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of drugs used to treat type 2 diabetes, have a beneficial effect on these mechanisms. Randomized clinical trials have shown that SGLT2i improves cardiac function and reduces the rate of cardiovascular and renal events. SGLT2i also increase mitochondrial efficiency, reduce oxidative stress and inflammation, and strengthen tissues. These findings suggest that SGLT2i hold great potential for the treatment of CVD. Furthermore, they are proposed as anti-aging drugs; however, rigorous research is needed to validate these preliminary findings.

The association between the size of adipocyte-derived extracellular vesicles and fasting serum triglyceride-glucose index as proxy measures of adipose tissue insulin resistance in a rat model of early-stage obesity.

Introduction: Obesity is a complex disease that predisposes individuals to cardiometabolic alterations. It leads to adipose tissue (AT) dysfunction, which triggers insulin resistance (IR). This suggests that people with obesity develop local IR first and systemic IR later. AT secretes extracellular vesicles, which may be physiopathologically associated with the development of IR. Our aim was to evaluate the effect of a high-fat diet on different parameters of adiposity in a rat model of early-stage obesity and to determine if these parameters are associated with markers of systemic IR. In addition, we sought to explore the relationship between fasting blood measures of IR (Triglycerides/High Density Lipoprotein-cholesterol [TAG/HDL-c] and Triglycerides-Glucose Index [TyG Index]) with the size of adipocyte-derived extracellular vesicles (adEV). Methods: We used a model of diet-induced obesity for ten weeks in Wistar rats exposed to a high-fat diet. Final weight gain was analyzed by Dual X-ray absorptiometry. Visceral obesity was measured as epididymal AT weight. IR was evaluated with fasting TyG Index & TAG/HDL-c, and adEV were isolated from mature adipocytes on ceiling culture. Results: In the high-fat diet group, glucose and triglyceride blood concentrations were higher in comparison to the control group (Log2FC, 0.5 and 1.5 times higher, respectively). The values for TyG Index and adEV size were different between the control animals and the high-fat diet group. Multiple linear regression analyses showed that adEV size can be significantly associated with the TyG Index value, when controlling for epididymal AT weight. Conclusion: Our results show that lipid and glucose metabolism, as well as the size and zeta potential of adEV are already altered in early-stage obesity and that adEV size can be significantly associated with liver and systemic IR, estimated by TyG Index.

Nuclear receptors behind the therapeutic effects of plant sterols on metabolism: A review.

Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms.

Effects of peptides and probiotics supplementation via diet on blood parameters and growth performance of Piaractus brachypomus during the growth-out phase.

Background: There is no evidence of peptides-probiotics symbiosis as supplements in aquafeeds. Aim: To evaluate the effect of peptides and probiotics supplementation via diet on blood parameters and growth performance of juvenile Piaractus brachypomus, an Amazonian fish, during the growth-out phase. Methods: 120 juvenile P. brachypomus (242.77 g) were placed into twelve 200-l tanks (10 fish/tank), housed in an indoor open system with constant water renovation (flow rate:1.50 l/minute). The experiment used a completely randomized design with a 4 × 5 factorial arrangement [4 doses of supplementation (CD: commercial diet; PepD: CD+1.50% of peptides per CD weight; ProD: CD+40.00 ml of activated probiotics per kg of diet (Lactobacillus spp., Rhodopseudomonas spp., Saccharomycetes spp.); PepProD: CD+Pep+Pro); 5 sampling times (zero, second, fourth, sixth, and eighth week); n = 3]. Fish were fed twice a day at a feeding rate of 1% of body weight. At each sampling time, blood was collected and fish were measured for growth performance analysis. Data were analyzed by using two-way ANOVA and Tukey's test (p < 0.05). Results: The values of hematocrit (18.31%), leukocytes (1,216.67 mm3), neutrophils (81.27%), lymphocytes (18.73%), albumin (1.08 g/dl), relative growth rate (1.002%/day), and the Fulton allometric condition factor (2.03) remained constant throughout the experiment (p > 0.05). Plasma glucose decreased for all fish in the second week (59.56 mg/dl); then, that level increased in fish fed with the CD (89.00 mg/dl), while fish fed with PepD, ProD, and PepProD showed constant values (57.22 mg/dl). The plasma protein levels were constant in fish fed with the PepD and PepProD, (p > 0.05), while fish fed with the CD and ProD showed non-constant and higher values. At the end of the trial, fish fed with the PepProD showed the highest weight gain and the lowest feed conversion rate (39.66 g; 0.97). Conclusion: It is possible to maintain the stability of plasma glucose and plasma protein by supplementing diets with peptides, but the peptides-probiotics symbiosis administrated via diet contributes to maintaining the stability of plasma glucose and plasma protein and to improve the growth performance of juvenile P. brachypomus during the growth-out phase.

Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Sodium-Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome.

Metabolic syndrome (MetS) is a multifactorial condition that significantly increases the risk of cardiovascular disease and chronic kidney disease (CKD). Recent studies have emphasized the role of lipid dysregulation in activating cellular mechanisms that contribute to CKD progression in the context of MetS. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy in improving various components of MetS, including obesity, dyslipidemia, and insulin resistance. While SGLT2i have shown cardioprotective benefits, the underlying cellular mechanisms in MetS and CKD remain poorly studied. Therefore, this review aims to elucidate the cellular mechanisms by which SGLT2i modulate lipid metabolism and their impact on insulin resistance, mitochondrial dysfunction, oxidative stress, and CKD progression. We also explore the potential benefits of combining SGLT2i with other antidiabetic drugs. By examining the beneficial effects, molecular targets, and cytoprotective mechanisms of both natural and synthetic SGLT2i, this review provides a comprehensive understanding of their therapeutic potential in managing MetS-induced CKD. The information presented here highlights the significance of SGLT2i in addressing the complex interplay between metabolic dysregulation, lipid metabolism dysfunction, and renal impairment, offering clinicians and researchers a valuable resource for developing improved treatment strategies and personalized approaches for patients with MetS and CKD.

Culture of Bovine Aortic Endothelial Cells in Galactose Media Enhances Mitochondrial Plasticity and Changes Redox Sensing, Altering Nrf2 and FOXO3 Levels.

Understanding the complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all of the main metabolic pathways. When glucose is replaced by galactose, cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as redox control is not well documented, particularly in endothelial cells, where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show a higher mitochondrial oxidative capacity, a more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main redox regulators and found that bovine aortic endothelial cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those in glucose-containing media. Thus, cultures of endothelial cells in a galactose-containing medium may provide a more suitable target for the study of in vitro mitochondrial-related processes than those in glucose-containing media; the medium deeply influences redox signaling in these cells.