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Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

Polycystic ovary syndrome (PCOS) is the main endocrine disorder in women of reproductive age worldwide. This condition is often associated with various metabolic alterations that contribute to the development of metabolic syndrome (MetS). Recent research suggests that branched-chain amino acid (BCAA) dysregulation is observed in PCOS. This study aims to investigate the relationship between dietary patterns, body composition, metabolic analytes, and serum amino acid levels in Mexican women with PCOS. Utilizing a cross-sectional design, we found that both study groups, PCOS (n = 24) and PCOS + MetS (n = 21), exhibited increased relative fat mass and dietary habits characterized by high simple sugar intake and low protein consumption, correlating with levels of relative fat mass and leptin. Notably, serum concentrations of BCAAs and glutamic acid were significantly elevated in the PCOS + MetS group. Our findings suggest that a metabolic approach may enhance the prediction and management of MetS in women with PCOS, highlighting the importance of dietary interventions in this population. [ABSTRACT FROM AUTHOR]

Excessive consumption of fat and carbohydrates, together with a decrease in traditional food intake, has been related to obesity and the development of metabolic alterations. Ramon seed is a traditional Mayan food used to obtain Ramon flour (RF) with high biological value in terms of protein, fiber, micronutrients, and bioactive compounds such as polyphenols. However, few studies have evaluated the beneficial effects of RF. Thus, we aimed to determine the metabolic effects of RF consumption on a high-fat-diet-induced obesity mouse model. We divided male BALB/c mice into four groups (n = 5 each group) and fed them for 90 days with the following diets: Control (C): control diet (AIN-93), C + RF: control diet adjusted with 25% RF, HFD: high-fat diet + 5% sugar in water, and HFD + RF: high-fat diet adjusted with 25% RF + 5% sugar in water. The RF prevented the increase in serum total cholesterol (TC) and alanine transaminase (ALT) that occurred in the C and HFD groups. Notably, RF together with HFD increased serum polyphenols and antioxidant activity, and it promoted a decrease in the adipocyte size in white adipose tissue, along with lower hepatic lipid accumulation than in the HFD group. In the liver, the HFD + RF group showed an increase in the expression of β-oxidation-related genes, and downregulation of the fatty acid synthase (Fas) gene compared with the HFD group. Moreover, the HFD + RF group had increased hepatic phosphorylation of AMP-activated protein kinase (AMPK), along with increased nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 2 (SOD2) protein expression compared with the HFD group. Thus, RF may be used as a nutritional strategy to decrease metabolic alterations during obesity.

Hepatic Sodium Taurocholate cotransporter polypeptide (NTCP1) captures approximately 80% of the conjugated bile acids that come from the enterohepatic circulation. Transcriptionally, NTCP1 expression is activated by an RAR/RXR heterodimer, which is repressed by SHP when intracellular bile acids are high. In addition, NTCP1 activity is post-translational modulated by phosphorylation. However, whether NTCP1 could be regulated by acetylation is unknown. A bioinformatic analysis for the mouse NTCP1 protein sequence showed potential lysine acetylation sites. Thus, we evaluated taurocholate uptake in hepatocytes incubated with NAM, which induced a two-fold increase in the content of acetylated proteins. Interestingly, taurocholate uptake was reduced by 50% in hepatocytes incubated with NAM. These results demonstrate that acetylation mediates taurocholate uptake in hepatocytes possibly through modulation of NTCP1 activity.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR. [ABSTRACT FROM AUTHOR]

ObjectiveObesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity.Research design and methods45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation.ResultsIn the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5′-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of β-oxidation and ω-oxidation, acyl-carnitines and ketone bodies.ConclusionsChange in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.

During gestation and lactation, a series of metabolic changes that are affected by the diet occurs in various organs of the mother. However, little is known about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the expression of metabolic genes in the mother. Therefore, the purpose of this work was to study the effect of consuming different percentages of DP/DCH, specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue during gestation and lactation in dams. While the amount of weight gained during gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained their weight during lactation. In the mammary gland, the expression of the genes involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased, and the expression of the genes involved in protein synthesis, such as mTOR1, and the phosphorylation of its target protein, S6K, were also increased throughout pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver and adipose tissue, the expression of the genes and proteins involved in lipid metabolism was dependent on the proportion of DP/DCH. The consumption of a low-protein/high-carbohydrate diet increased the expression of lipogenic genes in the liver and adipose tissue and the amount of lipid deposition in the liver. Conversely, the consumption of a high-protein/low-carbohydrate diet increased the expression of genes involved in amino acid oxidation in the liver during gestation. The metabolic adaptations reflected by the changes in the expression of metabolic genes indicate that the mammary gland has a priority for milk synthesis, whereas the adaptations in the liver and adipose tissue are responsible for providing nutrients to the mammary gland to sustain milk synthesis.

SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent 22Na+ uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent 22Na+ uptake by 34%. The reduction of SMCT1 activity by SGK1 depends on its kinase activity, and it was observed that the coinjection of SMCT1 with S442D-SGK1 (a constitutively active mutant) decreased the KIC-dependent 22Na+ uptake by 50%. In contrast, an SMCT1 coinjection with K127M-SGK1 (an inactive mutant) had no effect on the KIC-dependent Na+ uptake. The decreasing SMCT1 function by insulin or SGK1 was corroborated by measuring [1-14C]acetate uptake and the electric currents of SMCT1-injected oocytes. Previously, we found that SMCT2/Slc5a12-mRNA, but not SMCT1/Slc5a8-mRNA, is present in zebrafish pancreas (by in situ hybridization); however, SLC5a8 gene silencing was associated with the development of human pancreatic cancer. We confirmed that the mRNA and protein of both transporters were present in rat pancreas using RT-PCR with specific primers, Western blot analysis, and immunohistochemistry. Additionally, significant propionate-dependent 22Na+ uptake occurred in pancreatic islets and was reduced by insulin treatment. Our data indicate that human SMCT1 is regulated by insulin and SGK1 and that both SMCTs are present in the mammalian pancreas. [ABSTRACT FROM AUTHOR]

BACKGROUND: Histoplasmosis is a deep mycosis that affects multiple organs, including the skin and bone marrow. CLINICAL CASE: A 36-year-old male patient diagnosed with HIV and cutaneous histoplasmosis, which manifested as a disseminated dermatosis on the neck, trunk, upper and lower extremities, characterized by papular neoformations of 1-3 mm in diameter, some of them umbilicated, erythematous and hyperpigmented, light brown in color. He had a good response to treatment with amphotericin B and later with itraconazole, as well as antiretroviral therapy. CONCLUSIONS: Histoplasmosis is a common opportunistic mycosis in patients with HIV infection and acquired immunodeficiency syndrome (AIDS), which usually starts nonspecifically and may subsequently presents as a disseminated variant. The skin lesions show a heterogeneous morphology, such as umbilicated papules, nodules, vegetating plaques and/or macules. Amphotericin B and itraconazole are first-line treatments. [ABSTRACT FROM AUTHOR]

SMCTs move several important fuel molecules that are involved in lipid, carbohydrate, and amino acid metabolism, but their regulation has been poorly studied. Insulin controls the translocation of several solutes that are involved in energetic cellular metabolism, including glucose. We studied the effect of insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition of insulin reduced α-keto-isocaproate (KIC)-dependent 22 Na + uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent 22 Na + uptake by 34%. The reduction of SMCT1 activity by SGK1 depends on its kinase activity, and it was observed that the coinjection of SMCT1 with S442D-SGK1 (a constitutively active mutant) decreased the KIC-dependent 22 Na + uptake by 50%. In contrast, an SMCT1 coinjection with K127M-SGK1 (an inactive mutant) had no effect on the KIC-dependent Na + uptake. The decreasing SMCT1 function by insulin or SGK1 was corroborated by measuring [1- 14 C]acetate uptake and the electric currents of SMCT1-injected oocytes. Previously, we found that SMCT2/Slc5a12-mRNA, but not SMCT1/Slc5a8-mRNA, is present in zebrafish pancreas (by in situ hybridization); however, SLC5a8 gene silencing was associated with the development of human pancreatic cancer. We confirmed that the mRNA and protein of both transporters were present in rat pancreas using RT-PCR with specific primers, Western blot analysis, and immunohistochemistry. Additionally, significant propionate-dependent 22 Na + uptake occurred in pancreatic islets and was reduced by insulin treatment. Our data indicate that human SMCT1 is regulated by insulin and SGK1 and that both SMCTs are present in the mammalian pancreas.