Beatriz E. Martínez-Carrillo

Type 2 diabetes, PUFAs, and vitamin D: their relation to inflammation.

Chronic diseases have become one of the most important public health problems, due to their high costs for treatment and prevention. Until now, researchers have considered that the etiology of Type 2 diabetes mellitus (T2DM) is multifactorial. Recently, the study of the innate immune system has offered an explanation model of the pathogenesis of T2DM. On the other hand, there is evidence about the beneficial effect of polyunsaturated fatty acids (PUFA) n-3 and n-6 in patients with chronic inflammatory diseases including diabetes. Furthermore, high vitamin D plasmatic concentrations have been associated with the best performance of pancreatic β cells and the improving of this disease. In conclusion, certain fatty acids in the adequate proportion as well as 25-hydroxivitamin D can modulate the inflammatory response in diabetic people, modifying the evolution of this disease.

Diet, exercise and gut mucosal immunity.

Diet and exercise are primary strategies recommended for the control of the obesity epidemic. Considerable attention is being paid to the effect of both on the immune system. However, little research has been done on the effect of diet, nutrients or exercise on the mucosal immune system. The gastrointestinal tract (gut) is not only responsible for the entry of nutrients into the organism, but also for triggering the primary immune response to orally ingested antigens. The gut-associated lymphoid tissue contains a large amount of immune cells, disseminated all along the intestine in Peyers patches and lamina propria. Specific nutrients or their combinations, as well as the microflora, are capable of modulating the immune system through cell activation, production of signalling molecules or gene expression. We have observed an increase in T-cells as well as a decrease in B-cells from Peyers patches, induced by diets high in fats or carbohydrates in Balb/c mice. It has also been demonstrated that exercise modulates the immune system, where moderate levels may improve its function by increasing the proliferation of lymphocytes from various sites, including gut-associated lymphoid tissue, whereas exhaustive acute exercise may cause immunosuppression. High-fat diets combined with exercise are able to induce an increase in CD3+ lymphocytes due to increased CD8+ cells and a decrease in B-cells. Explanations and consequences of the effects of diet and exercise on the gut mucosal immunity are still being explored.

Repeated Restraint Stress Reduces the Number of IgA-Producing Cells in Peyer’s Patches

The few reports that have analyzed the effects of stress on the immune cells of the intestinal mucosa or the functions of these cells have tended to focus on S-IgA levels in saliva, and these studies have shown contradictory results. The principal objective of this study was to analyze the effects of repeated restraint stress on the number and distribution of immune cells in Peyer’s patches (PPs) as well as the effects of glucocorticoid and catecholamine administration on the same stress-related parameters. Upon analyzing the effect of repeated restraint stress on PPs, it was found that there was no modification in the morphological structure of the PPs but that restraint stress reduced the total number of lymphocytes and the number of CD8+ T cells, B cells, and plasma cells in PPs. Only at the site of PPs where IgA-producing plasma cells are most numerous (the dome) was a decrease found in this type of cell. These effects were due at least in part to the effect of glucocorticoids and catecholamines. Since IgA produced in PPs is a natural antibody that impedes bacterial infections, repeated stress may favor the entry of pathogens through the intestine.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients

Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.

Effect of Diet and Exercise on the Peripheral Immune System in Young Balb/c Mice

Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise.

Are immunoglobulin concentrations associated with the body composition of adolescents

The aim of this study was to analyze the association between serum concentrations of immunoglobulins (Ig) A, G, and M and body composition of adolescents from Mexico. Informed consent was obtained from parents and assent was obtained from the adolescents for the evaluation of 125 adolescents from the Capital city of Toluca and the adjacent semiurban county of Lerma de Villada. Height, weight, waist, and hip circumference were measured by trained personnel. Body mass index and waist:hip ratio were calculated from these measurements, whereas body fat (BF) was calculated from tricipital and subscapular skinfolds and measured by bioelectrical impedance. Serum concentrations of Ig were determined by nephelometry. Data were analyzed by independent samples t test and Pearson correlations. Subjects were mainly females (71.2%), with a mean age of 16.8 years (+/-0.8). No differences were reported in all indicators by weight or BF between gender. Female participants had higher Ig concentrations than males (IgG t = 2.24, p = 0.027; IgA t = 2.05, p = 0.043; IgM t = 4.49, p < 0.001). Positive correlations were reported for IgA and IgM with tricipital skinfold (r = 0.192, p = 0.041; and r = 0.221, p = 0.018, respectively) and for total BF by bioimpedance (r = 0.243, p = 0.009). Ig concentrations do not seem to be affected by overweight, obesity, or excessive or central BF in adolescents.

The effect of a high fat or high carbohydrate diet on the immune system of young Balb/c mice

Inappropriate lifestyles have shifted dietary patterns from natural to processed foods as well as to high fat, high simple carbohydrates and low fibre diets. High fat or high carbohydrate diets have different metabolic effects and may cause diseases such as diabetes, atherosclerosis or obesity. These effects have also been observed on some areas of the immune system; however, little is known about changes caused by diet on the gut mucosal immunity, which is the first point of entry for dietary components. The objective of this study was to evaluate the effect of a high fat (HFD) or a high carbohydrate (HCD) diet on T-cells from lamina propria in a murine model. We used three groups (n = 8) of 21-day-old Balb/c mice; Control, HFD, HCD (Table 1); small intestine (Peyer’s patches were eliminated) samples were obtained after 9 weeks. After purification of T-cells, lymphocytes were cultivated with phytohaemagglutinin (PHE) for 48 h, supernatants were collected for determination of IL-2, IL-4, IL-5, TNF-a and IFN-g , and T-cell populations using anti-CD3 + , CD4+ and CD8+ were analysed by flow cytometry. HFD mice had lower T-CD3 + (30.92 3.62%), T-CD4 + (1.48 0.33%) and T-CD8 + (3.46 1.87%), while HCD mice had increased values of all T-CD3 + (56.36 6.76%), T-CD4 + (20.24 4.5%) and T-CD8 + (26.93 4.67%) when compared to Controls (44.34 3.84%, 19.98 3.59% and 22.29 3.82%, respectively) (Fig. 1). Data were statistically different by ANOVA (F = 83.38, P<0.0001). Cytokine secretion was found increased in both HCD (IL-2 5.26 1.68 pg/ml, IL-5 16.65 2.02 pg/ml and TNF-a 14.52 2.35 pg/ml) and HFD (IL-2 4.60 0.930 pg/ml, IL-5 10.78 2.32 pg/ml, TNF-a 18.13 2.05 pg/ml; compared to controls (3.03 0.568, 8.27 1.25 and 9.28 1.88, respectively). HFD is able to affect more drastically the mucosal immune system with a decrease in all T-cell populations and a higher TNF-a secretion. HCD on the other hand, increases T lymphocytes as well as IL-2 and IL-5. We can conclude that a high-fat diet has a more deleterious effect on the immune system in mice. This project was financed by Universidad Autónoma del Estado de México.

Association Between Cardiovascular Risk Factors and Stress Hormones With Cognitive Performance in Mexican Adolescents

Objective The objective of this study was to determine whether cardiovascular disease (CVD) risk factors and stress hormones are associated with cognitive performance in Mexican adolescents. Methods This was a cross-sectional study including 139 Mexican adolescents 10-14 years old. Participants were divided into three categories: 0, 1-2, and ≥3 CVD risk factors. These factors included: high-density lipoprotein-cholesterol (HDL-C) <40 mg/dl; waist circumference (WC) ≥90th percentile for age and sex, systolic or diastolic blood pressure ≥90th percentile for age, sex, and height; and triacylglycerols (TGs) ≥110 mg/dl. Low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C), total cholesterol, cortisol, and plasma catecholamines were measured as well. Furthermore, attention, memory, and executive functions were evaluated using a validated test for Spanish-speaking individuals (Neuropsi). Results Adolescents in the three risk categories did not show significant differences in Neuropsi test performance tasks; however, they presented different lipid and plasma norepinephrine concentrations. TG and VLDL-C were inversely associated with memory (r = -0.19, **p < .01). Multivariate regression analysis showed consistently that TG/HDL-C ratio was inversely related to attention-memory general score (standardized β = -0.99, t = -2.30, p = .023), memory (standardized β = -0.83, t = -2.08, p = .039), and attention-executive functions (standardized β = -1.02, t = -2.42, p = .017). Plasma epinephrine levels presented an inverse and weak relation to the attention-executive functions score (standardized β = -0.18, t = -2.19, p = .030). Conclusions Cognitive performance is not completely dependent on the accumulation of risk factors, but instead on the combination of strong predictors of CVD like waist to height ratio, TG/HDL-C, and VLDL-C. Plasma norepinephrine and epinephrine have a stronger association with cognition and CVD risk than dopamine and cortisol.

Effect of Supplementation with n-3 Fatty Acids Extracted from Microalgae on Inflammation Biomarkers from Two Different Strains of Mice

Background Diabetes mellitus is considered a chronic noncommunicable disease in which inflammation plays a main role in the progression of the disease and it is known that n-3 fatty acids have anti-inflammatory properties. One of the most recent approaches is the study of the fatty acids of microalgae as a substitute for fish oil and a source rich in fatty acids EPA and DHA. Objective To analyze the effect of supplementation with n-3 fatty acids extracted from microalgae on the inflammatory markers from two different strains of mice. Methods Mice of two strains, db/db and CD1, were supplemented with n-3 fatty acids extracted from microalgae in lyophilized form and added to food; the experiment was carried out from week 8 to 16 of life. Flow cytometry was performed to determine the percentage of TCD4+ cells producing Th1 and Th2 cytokines. Results Supplementation with microalgae fatty acids decreased the percentage of TCD4+ cells producing IFN-γ and TNF-α and increased the ones producing IL-17A and IL-12 in both strains; on the other hand, supplementation decreased percentage of TCD4+ cells producing IL-4 and increased the ones producing TGF-β. Conclusions Microalgae n-3 fatty acids could be a useful tool in the treatment of diabetes as well as in the prevention of the appearance of health complications caused by inflammatory states.

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice

Background The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. Objective To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. Material and Methods 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α). Results Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyers patches, but only Stevia in lamina propria. Conclusion Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa.