Insulin Concentrations Research Articles

The Concentration of Liver-Expressed Antimicrobial Peptide 2 in Human Milk and Infant Plasma Is Positively Associated with Adiposity and Body Weight in the First Year of Life

BackgroundThe liver-expressed antimicrobial peptide 2 (LEAP2) is a recently recognized anorectic and glucose-regulating hormone with an unknown role in lactation. ObjectivesThe objectives of this study were as follows: 1) to assess LEAP2 presence in human milk and putative associations with infant body weight and adiposity in the first year of life, 2) to evaluate the impact of maternal weight status on LEAP2 concentration, and 3) to explore the relationship between infant plasma LEAP2 concentration and body weight and adiposity. MethodsThis prospective cohort observational study assessed LEAP2 concentration in plasma and milk from lactating women with normal weight (n = 26) or overweight or obesity (OW/OB, n = 26) at 6 mo postpartum and in 6-mo-old infant plasma, examining associations with metabolic and anthropometric variables at 6 mo and 1 y. Maternal plasma and milk leptin and insulin concentrations were also measured. LEAP2 expression in milk fat globules and single-cell-RNA-sequencing datasets was evaluated. ResultsLEAP2 was detected in all milk samples assessed (2.08 ± 0.65 ng/mL) and was positively associated with infant triceps (P = 0.022, Cohen f2 = 1.25) and subscapular (P = 0.008, f2 = 0.68) skinfolds at 1 y old. Maternal LEAP2 was positively associated with insulin (P = 0.005, f2 = 0.30) and prepregnancy body mass index (BMI) (P = 0.040, f2 = 0.17) and negatively associated with gestational weight gain (P = 0.008, f2 = 0.25) and postpartum weight retention (P = 0.036, f2 = 0.15). Maternal LEAP2 was higher in plasma (P = 0.039), but not milk of lactating women with OW/OB. Infant plasma LEAP2 (1.98 ± 0.28 ng/mL) was positively associated with weight (P = 0.004, f2 = 0.63), BMI (P = 0.049, f2 = 0.37), and weight-for-length (P = 0.024, f2 = 0.35) z-scores at 1 y old, predominantly in males. No evidence for LEAP2 mRNA expression was found in mammary cells. ConclusionsMilk LEAP2 is a bioactive component that plays a role in infant fat accretion in the first year of life. Although maternal LEAP2 responds to weight change in pregnancy and lactation, infant plasma LEAP2 might be involved in body weight regulation in early life.This trial was registered at clinicaltrials.gov as NCT05798676.

Effect of inulin from dahlia tubers (Dahlia variabilis) extract on insulitis severity and insulin expression in diabetic rats.

Dahlia (Dahlia variabilis), a widely cultivated ornamental plant in Indonesia, is known to contain 84.08% inulin in its tubers. Numerous studies have demonstrated the antidiabetic potential of inulin from various plant sources. However, most of the research is in the form of a mixture of inulin with other active substances, and no one has analyzed the effects of inulin derived from dahlia tubers. This study examines the effect of inulin from dahlia tuber extract on blood glucose levels, serum insulin expression, pancreatic tissue insulin expression, homeostatic model assessment of insulin resistance (HOMA-IR), and the extent of insulitis in diabetic rats. In this experimental study, 20 male Wistar rats were randomly allocated to five groups. Group I served as the control, Group II as the STZ-induced diabetic group, Group III as the STZ-induced diabetic group treated with inulin (0.5 g/kgBW), Group IV as the STZ induced diabetic group treated with inulin (1.0 g/kgBW), and Group V as the STZ-induced diabetic group treated with inulin (1.5 g/kgBW). The inulin was administered for 21 days. The degree of insulitis was evaluated using a scoring system, serum insulin concentration via ELISA, and insulin expression in the pancreas through immunohistochemistry. Administration of inulin from dahlia tubers significantly reduced serum glucose concentrations in diabetic rats. Notably, only inulin extracts at doses of 1 g/kgBW and 1.5 g/kgBW showed a significant reduction in insulitis and HOMA-IR index in diabetic rats, while the 0.5 g/kgBW inulin extract reduced insulitis without affecting HOMA-IR. Inulin extract administration did not affect insulin expression in serum or pancreatic tissue. Inulin from dahlia tuber can exert antidiabetic properties by improving insulin resistance and insulitis. These studies suggest the great potential of dahlia tubers as the source of inulin for prebiotic functional foods.

Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study

BackgroundNumerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.MethodsIndependent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.ResultsGenetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = − 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = − 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = − 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).ConclusionOur MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

Embryonic, Fetal, and Neonatal Complications in Infants of Diabetic Mothers: Insights from the Cincinnati Diabetes in Pregnancy Program Project Grant.

This study aimed to review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to the understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs). This is a retrospective review of all PPG work on glycemic control at different pregnancy time points and its association with embryonic, fetal, and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction, macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia, and polycythemia. We found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth whereby early growth delay was followed by enhanced fetal growth associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third-trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor. KEY POINTS: · Poor glycemic control during embryogenesis is a major risk factor for CMs.. · Magnesium deficiency might contribute to major malformations.. · Macrosomia is associated with poor glycemic control in the third trimester.. · Strict glycemic control reduces fetal and neonatal morbidity in pregnancies with insulin-dependent diabetes mellitus..

Likely causal effects of insulin resistance and IGF-1 bioaction on childhood and adult adiposity: a Mendelian randomization study

BackgroundCirculating insulin and insulin-like growth factor-1 (IGF-1) concentrations are positively correlated with adiposity. However, the causal effects of insulin and IGF-1 on adiposity are unclear.MethodsWe performed two-sample Mendelian randomization analyses to estimate the likely causal effects of fasting insulin and IGF-1 on relative childhood adiposity and adult body mass index (BMI). To improve accuracy and biological interpretation, we applied Steiger filtering (to avoid reverse causality) and ‘biological effect’ filtering of fasting insulin and IGF-1 associated variants.ResultsFasting insulin-increasing alleles (35 variants also associated with higher fasting glucose, indicative of insulin resistance) were associated with lower relative childhood adiposity (P = 3.8 × 10−3) and lower adult BMI (P = 1.4 × 10−5). IGF-1-increasing alleles also associated with taller childhood height (351 variants indicative of greater IGF-1 bioaction) showed no association with relative childhood adiposity (P = 0.077) or adult BMI (P = 0.562). Conversely, IGF-1-increasing alleles also associated with shorter childhood height (306 variants indicative of IGF-1 resistance) were associated with lower relative childhood adiposity (P = 6.7 × 10−3), but effects on adult BMI were inconclusive.ConclusionsGenetic causal modelling indicates negative effects of insulin resistance on childhood and adult adiposity, and negative effects of IGF-1 resistance on childhood adiposity. Our findings demonstrate the need to distinguish between bioaction and resistance when modelling variants associated with biomarker concentrations.

Investigation of Relationships between Intakes of Human Milk Total Lipids and Metabolic Hormones and Infant Sex and Body Composition.

Human milk (HM) composition, including metabolic hormones and lipids, is influenced by various factors, including lactation stage and, potentially, infant sex, which may affect infant body composition (BC) development. We aimed to: (a) characterize the longitudinal concentration and intake profiles of HM leptin, adiponectin, insulin, and total lipids; (b) determine if their concentrations and intakes differ by infant sex; and (c) explore the intakes relationships with the development of infant BC. Milk samples (n = 501) were collected from 82 mother-infant dyads during the first 6 months postpartum. Infant 24 h HM intake was measured, and the average cumulative HM component intakes were calculated. The statistical analysis used linear mixed modeling. Intakes of HM leptin, adiponectin, insulin, and total lipids increased to 1 month postpartum and then remained stable. HM intake and total lipids intake but not hormone intakes were positively associated with infant BC (fat-free mass, fat-free mass index, fat mass, fat mass index, percentage fat mass, and fat mass to fat-free mass ratio). HM component concentrations and intakes did not differ by sex. These findings advance our understanding of the temporal nature of HM components, emphasizing the role of infant 24 h HM and total lipids intake in development of infant lean and adipose tissue.

Postprandial Blood Glucose and Insulin Response in Healthy Adults When Lentils Replace High-Glycemic Index Food Ingredients in Muffins, Chilies and Soups.

This study aimed to assess postprandial blood glucose response (PBGR), relative glycemic response (RGR) and insulin response when 25 g available carbohydrates (AC) is replaced with cooked lentils in the formulation of muffins, chilies and soups. In randomized, crossover studies, healthy adults consumed foods containing 25 g AC from green lentils, red lentils or a control (wheat muffin, n = 24; rice chili, n = 24; potato soup, n = 20). Blood collected at fasting and at 15, 30, 45, 60, 90 and 120 min was analyzed to derive the incremental area under the response curve (iAUC) for glucose, insulin, RGR and maximum concentration (CMAX). Treatment effects were assessed with repeated measures ANOVA. A replacement of 25 g AC with green lentils significantly decreased glucose iAUC compared to chili and soup (p < 0.0001), but not muffin (p = 0.07) controls, while also eliciting a significantly lower insulin iAUC for all three foods (muffin p = 0.03; chili p = 0.0002; soup p < 0.0001). Red lentil foods significantly decreased glucose iAUC (muffin p = 0.02; chili p < 0.0001; soup p < 0.0001) compared to controls, with a significantly lower insulin iAUC for chili and soup (p < 0.0001) but not muffins (p = 0.09). The RGR for muffins, chilies and soups was 88, 58 and 61%, respectively, for green lentils, and 84, 48 and 49%, respectively, for red lentils. PBGR, insulin and RGR are decreased when lentils are incorporated into food products, providing credible evidence to promote carbohydrate replacement with lentil-based foods.

Fetal sex effects on maternal health can now be tested via randomization: A first-in-class illustration in cows on glucoregulatory outcomes

BackgroundThe maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship. ObjectiveTo demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes. MethodsHolstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis. ResultsWe demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05). ConclusionWe demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes.

The Impact of Thyroid Hormones on Cardiometabolic Risk in Children and Adolescents with Obesity, Overweight and Normal Body Mass Index (BMI): A One-Year Intervention Study.

Thyroid hormones regulate metabolism and have a major impact in maintaining cardiovascular homeostasis. The purpose of our study was to examine the relation of thyrotropin (TSH) and thyroid hormones with cardiometabolic parameters in children and adolescents with obesity, overweight, and normal body mass index (BMI) before and after the implementation of a comprehensive, multidisciplinary, personalized, lifestyle intervention program for 1 year. One thousand three hundred and eleven (n = 1311) children and adolescents aged 2 to 18 years (mean age ± SD: 10.10 ± 2.92 years) were studied prospectively. Patients were categorized as having obesity (n = 727, 55.45%), overweight (n = 384, 29.29%) or normal BMI (n = 200, 15.26%) according to the International Obesity Task Force (IOTF) cutoff points. All patients received personalized guidance on diet, sleep, and physical activity at regular intervals throughout the 1-year period. Detailed clinical evaluation and hematologic, biochemical and endocrinologic investigations were performed at the beginning and the end of the study. Subjects with obesity had a more adverse cardiometabolic risk profile than subjects with overweight and normal BMI on both assessments. At initial evaluation, total T3 concentrations were positively associated with uric acid and HbA1C, and free T4 concentrations were negatively associated with insulin concentrations, while there was no association between TSH concentrations and cardiometabolic risk parameters. Following the 1 year of the multidisciplinary, lifestyle intervention program, the concentrations of lipids, HbA1C, ALT, and γGT improved significantly in all subjects. Changes in TSH concentrations were positively associated with changes in systolic blood pressure (SBP), glucose, triglycerides, and cholesterol concentrations. Changes in free T4 concentrations were negatively associated with changes in cholesterol and insulin concentrations. Furthermore, changes in T3 concentrations were positively associated with changes in HbA1C, glucose, uric acid, and triglyceride concentrations. These findings indicate that in children and adolescents with overweight and obesity, thyroid hormones are associated with indices conferring cardiometabolic risk.

Metabolically healthy obesity in adults with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is characterized by increased concentrations of circulating fibroblast growth factor 23 (FGF-23) resulting in phosphate wasting, hypophosphatemia, atypical growth plate and bone matrix mineralization. Epidemiologic studies suggest a relationship between FGF-23, obesity, and metabolic dysfunction. The prevalence of overweight and obesity is high in children with XLH. We aimed to evaluate the prevalence of obesity and metabolic complications in adults with XLH. We conducted a prospective cohort study in adult XLH patients from a single tertiary referral center. The proportion of patients with a BMI >25 kg/m2 was the main outcome measure. Body fat mass percentage (FM%) and adipose tissue surfaces were secondary outcome measures. Glucose homeostasis (plasma glucose and insulin concentrations after fasting and 2 hours after an oral glucose tolerance test) was explored in a subgroup of patients and compared with age-, sex-, and BMI-matched healthy controls. Among 113 evaluated patients, 85 (75%) were female and 110 (97%) carried a PHEX mutation. Sixty-three (56%) patients were overweight or obese, with a median BMI of 25.3 [IQR, 22.7; 29.2] kg/m2. BMI was correlated with FM%, abdominal and thigh subcutaneous and intra-abdominal adipose tissue surfaces. The prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes was not different between XLH patients and matched controls. The prevalence of overweight and obesity is high among XLH patients and is associated with excess fat mass. However, the prevalence of glucose homeostasis abnormalities is not increased in patients compared to healthy controls, suggesting that metabolically healthy overweight or obesity predominates.

Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Amphipathic KALA fusogenic peptide enhances absorption of insulin and calcitonin by pulmonary membranes of rats.

The aim was to investigate the absorption-enhancing effect (AEE) of lysine-alanine-leucine-alanine (KALA) repeating unit peptide upon pulmonary absorption of peptide and protein medicines among rats. Absorption of insulin and calcitonin in the lung was evaluated using varying concentrations of KALA peptide from 0.1% to 1.0% (w/v). The study also examined the lung damage caused by the KALA peptide. KALA peptide with various concentrations improved the absorption of insulin and calcitonin in the lungs. It also reduced glucose and calcium levels in the blood compared to the control, with the AEE increasing in a concentration-dependent manner due to the KALA peptide. In toxicity assays, test results for protein and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) did not show a significant increase in the presence of KALA peptide at various concentrations. This implies that the KALA peptide did not cause any membrane damage to lung tissues. In transmembrane electrical resistance (TEER) and permeability detection, a decrease in TEER value and an increase in papp value by the addition of KALA peptide indicated that KALA peptide had the ability to aid the drug delivery through epithelial cells via both paracellular and transcellular pathways. KALA peptides are suitable as an absorption enhancer at lower concentrations (below 1.0%, w/v) for improving the absorption of insulin and calcitonin from the lung with no observed toxic impact.

Production Responses of Multiparous Dairy Cattle with Differing Prepartum Muscle Reserves and Supplementation of Branched-Chain Volatile Fatty Acids

Periparturient dairy cattle undergo physiological adaptations to support fetal growth and colostrum synthesis in late gestation and milk production in early lactation. To support energy and protein demands dairy cattle mobilize body tissue reserves. The objective of this study was to determine the effects of prepartum skeletal muscle reserves and supplementation of branched-chain volatile fatty acids (BCVFA) on body composition measurements, metabolic markers related to health, protein, and energy status, and subsequent milk yield in multiparous dairy cows. Skeletal muscle reserves were assessed by 3 ultrasounds of the longissimus dorsi muscle depth (LDD) measured 42 d before expected calving (BEC), and cows (n = 48) were assigned to either high muscle (HM; > 4.6 cm) or low muscle (LM; ≤ 4.6 cm) groups. Cows were then randomly assigned to either control (CON) of soyhull pellets (80 g/d) or BCVFA treatment which contained isobutyrate (40 g/d), isovalerate (20 g/d), and 2-methylbutyrate (20 g/d) calcium salt products. Treatments were top dressed from 42 BEC until parturition, resulting in 4 combinations of muscle groups and treatments: HM-CON (n = 13), HM-BCVFA (n = 13), LM-CON (n = 11), and LM-BCVFA (n = 11). Measurements of the LDD, BW, and BCS were taken on the following days relative to calving -42, -35, -21, -7, 0, 7, 14, 21, 28. Weekly blood samples were taken to measure glucose, BHB, and insulin concentrations, and 5 of the blood sample time points were utilized to determine 3-methylhistidine and creatinine blood concentrations. Milk yield was recorded daily for the first 28 d of lactation, and samples were taken from both milkings once a wk for the first 4 wk to determine components. The statistical model included the fixed effects of treatment, group, time, their interactions, and the random effect of cow nested within group and treatment. Prepartum muscle mobilization varied between muscle groups, as LM cows accreted muscle prepartum, and HM cows mobilized muscle. The HM cows had higher milk fat, protein, lactose, and energy corrected milk yields. The BCVFA supplementation tended to increase blood glucose concentrations both prepartum and postpartum and decreased milk urea nitrogen concentrations. Higher prepartum skeletal muscle reserves improve productivity of early lactation cows likely due to differences in muscle mobilization, and BCVFA supplementation improves glucose dynamics during the transition period, which may improve the metabolic health of the periparturient dairy cow.

Leucine requirement determined in healthy young adult males using the indicator amino acid oxidation method

BackgroundPrevious studies proposed varying leucine requirements for adults ranging from 25 to 40 mg⋅kg−1⋅d−1, but often these studies did not test intakes exceeding 40 mg⋅kg−1⋅d−1. Data using the indicator amino acid oxidation (IAAO) method suggest a higher requirement of 55 mg⋅kg−1⋅d−1 on the basis of the total branched-chain amino acids requirement, but not leucine independently. ObjectivesThe IAAO method was used to determine the leucine requirement in healthy young adult males. MethodsTen healthy adult males (26.9 ± 1.87 y, mean ± SEM) were studied at 7 leucine intakes; each studied over a 3-d period. Following 2-d of preadaptation to adequate protein intake (1.0 g⋅kg−1⋅d−1), subjects received experimental diets containing the randomly assigned test leucine intake (10, 20, 30, 40, 50, 65, and 75 mg⋅kg−1⋅d−1) for 8 h. The rate of the release of 13CO2 from the oxidation of L-[1-13C]phenylalanine (F13CO2) was measured on the third day, and the leucine requirement was determined using mixed-effect change-point regression and the F13CO2 data in R. The 95% confidence interval was calculated using parametric bootstrap. The effect of leucine intake on the concentration of plasma amino acids, insulin, and glucose were assessed using repeated measures analysis of variance and linear mixed effects. ResultsThe mean leucine requirement was 33.6 mg⋅kg−1⋅d−1 with a lower and upper 95% confidence of 26.16, 41.04 mg⋅kg−1⋅d−1. Higher leucine intakes were associated with increased plasma leucine, and decreased valine, isoleucine, and serine concentrations. ConclusionsThe leucine requirement of young adult males is ∼34 mg⋅kg−1⋅d−1, which aligns with previously published tracer balance experiments.This trial was registered at http://clinicaltrials.gov (https://clinicaltrials.gov/study/NCT05394155?term=leucine%20young%20adult&rank=1) as NCT05394155.

Evidence of obesity-induced inflammatory changes in client-owned cats.

Insulin resistance and type 2 diabetes mellitus are common health issues in obese (OB) cats. In humans, obesity leads to alterations in adipokine and proinflammatory cytokine secretion, causing persistent inflammation. The inflammatory impact of obesity in cats remains unproven. This study investigated associations between obesity and inflammatory and metabolic changes in three groups of client-owned Brazilian domestic shorthair cats: naturally lean, overweight (OW), and OB. Cats from the Veterinary Hospital of Professor Sylvio Barbosa e Cardoso (FAVET/UECE) were clinically evaluated. Blood samples were collected for hematological and biochemical profile measurements, and part of the serum was used for measuring adipokine and inflammatory cytokines using sandwich enzyme-linked immunosorbent assay. In both the OW and OB groups, serum cholesterol and insulin concentrations increased, while triglyceride concentrations were notably elevated in the OB group. In the OW and OB groups, serum adiponectin, tumor necrosis factor-α, and interleukin-1β levels were elevated, and leptin levels were significantly higher in the OB group. This study is the first in Brazil to reveal increased serum levels of inflammatory markers in OW and OB client-owned felines. OW cats exhibited higher proinflammatory marker levels, implying obesity-induced inflammation.

The injection of maternal B complex vitamin during the transition period: The impact on performance, thyroid hormones levels and immunological parameters in the Sannen goats and their kids, as well as the faeces status of newborn kids.

It is proven that B vitamins through promote a wide range of metabolic pathways in animals as cofactors improve animal performance. This study was conducted to investigate the impacts of maternal B complex vitamin injection on performance and plasma parameters in goats and their offspring, as well as the faeces status of newborn kids. In this research, the pregnant goats (3 years old) were randomly divided into two groups: the control group (without B complex vitamin injection) and the B complex vitamin group (5mL B complex vitamin injection per animal). The animals were injected with 5mL B complex vitamin twice during the transition period (5 weeks pre- and 5 weeks post-kidding). The goats during the transition period and kids on days 10, 20 and 30 were weighed. Feed intake by goats and consumption of milk and starter in kids were recorded daily. The dry matter digestibility by kids was tested by collecting samples of faeces and feed for 5 days in the last week. Chemical analysis was determined using the AOAC method. The kids' faeces were prepared daily during the study. The blood samples of goats and newborn kids were taken 7 days after kidding. Then, levels of B group vitamin, as well as concentrations of liver enzymes, thyroid hormones and immunological parameters, were determined in plasma of goat and their offspring. In addition, concentrations of glucose and insulin were measured in goat plasma (Asadi et al., 2024). According to results, the performances of goats and their offspring, as well as kids' faeces status, were improved by maternal B complex vitamin injection (p<0.0001). The levels of cobalamin, pyridoxine, thiamine, folic acid, nicotinic, pantothenic and unconjugated pteridine increased in the plasma of goats and their kids in the B complex vitamin group compared with the control group during the transition period (p<0.0001). Injection of maternal B complex vitamin raised the plasma levels of triiodothyronine and tetraiodothyronine, immunoglobulin G and immunoglobulin M in goats and their offspring (p<0.0001). Higher levels of glucose and lower levels of insulin were determined in the goats injected with B complex vitamin (p<0.0001). These results suggest that maternal B complex vitamin injection is required for the improvement of performance, health status and the blood plasma parameters in pregnant goats and their kids.

Replacing Cereal with Ultraprocessed Foods in Pig Diets Does Not Adverse Gut Microbiota, L-glutamate Uptake, or Serum Insulin

BackgroundUsing ultraprocessed food (UPF) to replace traditional feed ingredients offers a promising strategy for enhancing food production sustainability. ObjectiveTo analyze the impact of salty and sugary UPF on gut microbiota, amino acids uptake, and serum analytes in growing and finishing pig. MethodsThirty-six Swiss Large White male castrated pigs were assigned to 3 experimental diets: 1) standard (ST), 0% UPF; 2) 30% conventional ingredients replaced by sugary (SU) UPF; and 3) 30% conventional ingredients replaced by salty (SA) UPF. The next-generation sequencing was used to characterize the fecal microbiota. Transepithelial electrical resistance and the active uptake of selected amino acids in pig jejuna were also evaluated. Data were enriched with measurements of fecal volatile fatty acids and serum urea, minerals, and insulin. All data analyses were run in R v4.0.3. The packages phyloseq, vegan, microbiome, and microbiomeutilities were used for microbiota data analysis. The remaining data were analyzed by analysis of variance using linear mixed-effects regression models. ResultsThe UPF did not affect fecal microbiota abundance or biodiversity. The Firmicutes to Bacteroidetes ratio remained unaffected. SU-induced increase in the Anaerostipes genus suggested altered glucose metabolism, whereas SA increased the abundance of CAG-352 and p-2534-18B. No effects on fecal volatile fatty acids were observed. Assumptions of UPF negatively affecting small intestinal physiology were not supported by the measurements of transepithelial electrical resistance in pigs. Active amino acids uptake tests showed potential decrease in L-glutamate absorption in the SA compared with the SU diet. Blood serum analysis indicated no adverse effects on urea, calcium, magnesium, or potassium concentration but the SU group resulted in a lower blood serum insulin concentration at the time of blood collection. ConclusionsWhen incorporated at 30% into a standard growing finishing diet for pigs, UPF does not have detrimental effects on gut microbiota, intestinal integrity, and blood mineral homeostasis.

Prevalence of insulin dysregulation in the non-obese stock-type horse and relationship with morphometric neck measurements

Insulin dysregulation (ID), core to equine metabolic syndrome, may present without obesity. Testing for ID risk is commonly based on breed and obese phenotype but might be valuable for non-obese stock-type horses. This study aimed to determine the prevalence of ID in non-obese stock-type horses and evaluate if morphometric neck measurements (MNM) correlate with ID. Sixty-two, non-obese (BCS 5, range 2.5-6/9) stock-type horses were assessed for MNM: neck circumference at 25%, 50% (NC50), and 75% (NC75) length, and crest height. An oral sugar test (OST; 0.15 mL/kg BW corn syrup) was performed with blood taken pre- and 60 min post-OST for insulin (PREI, POSTI) and glucose (PREG, POSTG). Insulin dysregulation was defined as insulin concentration > 45 µIU/mL POSTI. Three of 62 horses were ID (4.8%; 95% CI 1.0%-13.5%). Horses with ID had greater PREG (121.0 ± 7.56 vs. 105.3 ± 1.72 mg/dL; LS means ± SEM; P = 0.04) and PREI (15.7 ± 2.63 vs. 10.5 ± 0.59 µIU/mL; P = 0.05) than normal responders. Mares had greater PREI than geldings (11.7 ± 0.76 vs. 9.4 ± 0.89 µIU/mL; P = 0.04). Stepwise regression indicated a weak relationship with crest height and POSTG (y = 51.27 + (0.88 x NC50); R2 = 0.09; P = 0.02). Post-glucose correlated with NC50 (r = 0.30; P = 0.04) and NC75 (r = 0.29; P = 0.03). This study showed 4.8% of non-obese horses had ID, warranting testing irrespective of phenotype, but only a weak association between MNM and POSTG was found.

Anti-Obesity and Antidiabetic Effects of Fig (Ficus carica L.) Fermented Extract Using Lactobacillus plantarum BT-LP-01

This study aimed to assess the effect of fermented fig (Ficus carica L., FF) on obesity and diabetes in a mouse model. FF was cultured with the lactic acid bacterium Lactobacillus plantarum BT-LP-01 and isolated from fig peels. The antioxidant results demonstrated that FF exhibited DPPH and ABTS radical scavenging activities. In addition, FF showed high levels of total polyphenol and total flavonoids. Body and organ weight and dietary intake were significantly decreased in the FF groups compared to the HFD group. The FF group showed improved recovery in lipid metabolism and liver function compared to the HFD group. In addition, the FF group showed a significant decrease in serum C-P and insulin concentrations compared to the HFD group. FF-administered mice showed a dose-dependent recovery of fasting blood glucose and IPGTT and AUC levels compared to the HFD group. Furthermore, FF groups showed a decreased expression in FAS, C/EBPα, and FABP4, as well as significantly increased expression in ACC in the liver. This study demonstrates that FF is effective in reducing and inhibiting adipogenesis as well as lowering body weight, the blood glucose level, and lipid-related factors. These research findings demonstrate that FF is effective in treating obesity and diabetes.

Metabolic characteristics of different phenotypes in reproductive-aged women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder in reproductive-aged women. The study was designed to investigate the metabolic characteristics of different phenotypes in women with PCOS of reproductive age. A total of 442 women with PCOS were recruited in this cross-sectional study. According to different phenotypes, all women were divided into three groups: the chronic ovulatory dysfunction and hyperandrogenism group (OD-HA group, n = 138), the chronic ovulatory dysfunction and polycystic ovarian morphology group (OD-PCOM group, n = 161), and the hyperandrogenism and polycystic ovarian morphology group (HA-PCOM group, n = 143). The metabolic risk factors and prevalence rates of metabolic disorders among the three groups were compared. The body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) of women from the OD-HA group and HA-PCOM group were significantly higher than those of women from the OD-PCOM group (p < 0.05). The serum insulin concentration and homeostasis model assessment of insulin resistance (HOMA IR) at 2h and 3h after oral glucose powder in women from the OD-HA group and HA-PCOM group were significantly higher than those from the OD-PCOM group (p < 0.05). The serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in women from the OD-HA group and HA-PCOM group were significantly higher than those in women from the OD-PCOM group (p < 0.05). The prevalence rates of impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), insulin resistance (IR), metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and dyslipidemia of women with PCOS were 17.9%, 3.6%, 58.4%, 29.4%, 46.6%, and 43.4%, respectively. The prevalence rates of IGT, IR, MS, NAFLD, and dyslipidemia of women in the OD-HA group and HA-PCOM group were significantly higher than those of women in the OD-PCOM group (p < 0.05). T concentration (>1.67 nmol/L) and Ferriman-Gallwey (F-G) score (>3) significantly increased the risk of metabolic disorders in women with PCOS (p < 0.05). The phenotypes of OD-HA and HA-PCOM in women with PCOS were vulnerable to metabolic disorders compared to OD-PCOM. Thus, the metabolic disorders in women with PCOS especially those with the HA phenotype should be paid more attention in order to reduce long-term complications.