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 Na uptake by 29%. Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased the KIC-dependent 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 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-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 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.

Niacin and butyrate modulate cellular metabolism by several metabolic pathways. The niacin at therapeutic doses reduces blood lipid levels through the activation of its G protein receptor (GPR109), this vitamin is also a precursor of two important coenzymes involved in the cellular oxidation‐reduction processes (NAD(P)+/NAD(P)H). The consumption of butyrate in the diet produces a hypophagic effect in bovines. This effect was associated with an increase of leptin expression generating a loss of body weight. High fat diets supplemented with butyrate induce an improvement in insulin resistance in C57BL/6 mice. Butyrate also interacts with a G protein receptor (GPR 43). Both niacin and butyrate are substrates of the H+/monocarboxylate (MCT) and Na+/monocarboxylate (SMCT) transporters, these last being located in the lumen of the gastrointestinal tract and the proximal tubule of nephron. The physiological and molecular role of the receptors and transporters of the niacin and butyrate in body energy expenditure has been little studied.We used 80 C57BL/6 mice, 4 weeks old, divided into 8 groups (10 by group), were feed for 5 months with different diets with 10% kcal fat (control diets (C)) or with 45% kcal fat (high fat diet (HF)) both supplemented with 1% w/w niacin (N or HFN) or with 5% w/w butyrate (B or HFB) or with both monocarboxylates (BN; HFBN). Over the 5 month diet period were assessed weekly body weight changes with an analytical balance and monthly changes in body fat concentration with the EchoMRI ™ 4 in 1–500 small live animal body composition analyzers. The calorimetry analysis was performed with Columbus Instruments, Comprehensive Lab Animal Monitoring System: CLAMS. Several organs were extracted, including the kidneys for studies of protein and gene expression by WB and qPCR analysis respectively. The blood chemistry of the different groups was also evaluated. The renal function and physiology status of animals prior to slaughter was evaluated by the 24h urine collection in metabolic cages to evaluate various ions and metabolites.We observed that the co‐administration of butyrate and niacin prevents body weight gain. The calorimetric analysis showed that the energy expenditure in the HFBN group was higher than the HF group (P< 0.0001), similar situation was observed in the oxygen consumption (P< 0.039). The respiratory coefficient (RER) was 0.7 in HF and HFBN groups, suggesting an increase in fatty acid oxidation. In the body composition analysis the HFBN group gain a similar fat mass compared to C group with a maintained of fat free mass. The reduction of fat mass in HFBN group was significant compared with the HF group (P< 0.01). Interesting the mice groups that eat butyrate supplemented diets developed renal hyperplasia and hydronephrosis. The expressions of both SMCTs in the kidneys of BN and HFBN groups were significant reduced in contrast with C and HF groups. Also significant increment of UCP2 expression was observed in these groups.We conclude that the consumption of butyrate with niacin favors the oxidation of fatty acids and increased caloric expenditure that that modifies the expression of both SMCTs and UCP2 genes, however, as an adverse effect, butyrate diets causes a significant increase in serum creatinine and BUN and as observed in the histological analysis exist a loss of renal architecture. This effect is possibly caused by an obstruction in the renal tubules inducing a renal damage.Support or Funding InformationINCMSZ‐AI‐015 (CP) CONACYT 155700 (VR)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

La presencia de sobrepeso u obesidad es uno de los factores de riesgo modificables más importantes asociados con prediabetes y diabetes tipo 2 en todos los grupos de edad. En la actualidad, uno de cada tres niños y adolescentes mexicanos entre los seis y 19 años padece sobrepeso u obesidad. Los programas en el estilo de vida son prioritarios para impulsar el mantenimiento de un peso saludable y prevenir prediabetes y diabetes tipo 2. Objetivo: Evaluar el efecto de una intervención educativa en el estilo de vida para prevenir prediabetes o diabetes tipo 2 en niños mexicanos. Material y métodos: Piloto de un ensayo clínico controlado aleatorizado,

Introduction: New metabolomic biomarkers as Quantose™ IR and anthropometric measurements using bioelectrical impedance analysis (BIA) provide relevant information on patients with insulin resistance and prediabetes. QuantoseTM IR is a novel metabolomic test to assess insulin resistance for screening and monitoring. Establishing a correlation between these variables is useful in clinical practice and, to our knowledge, there are no published studies that explore the relationship between Quantose™ IR and anthropometric measurements using BIA in patients with prediabetes. Objective: To evaluate the correlation between Quantose™ IR and BIA anthropometric variables (fat mass, FM; fat mass index, FMI; and body mass index, BMI) in Mexican patients with prediabetes, overweight, and obesity. Materials and Methods: This is an observational, transversal analytic study in 135 patients of both genders between 20 and 65 years of age, BMI 25.0–34.9, with diagnosis of prediabetes. The Quantose™ IR test was performed as well as anthropometric measurements (FM, FMI, and BMI) using BIA taken with Inbody 230TM. Pearson’s correlations and independent sample t-tests were estimated with a significance level of p < 0.05. Results: 135 patients were studied; 77% were female, aged 46 years in average. The prevalence of insulin resistance by Quantose™ IR was 71.1%. A positive correlation was confirmed between Quantose™ IR and FM, FMI, and BMI (p < 0.05). Patients with altered Quantose™ IR had higher FM, FMI, and BMI (p < 0.05). Conclusion: The data here presented confirm the existence of a positive and statistically significant correlation between Quantose™ IR and anthropometric measurements using BIA. This information may be useful for diagnosis and treatment in prediabetic, overweight, and obese patients.