Modulation of Zinc Transporter Expressions by Additional Zinc in C2C12 Cells Cultured in a High Glucose Environment and in the Presence of Insulin or Interleukin-6.

Zn status has been related to various chronic diseases presenting oxidative stress and inflammation, such as type 2 diabetes. Zn supplementation has been suggested to be a potential coadjuvant in the management of this condition. Zn transporters constitute a key component in the maintenance of Zn homeostasis. Our aim was to evaluate the modulatory effect of additional Zn (10 or 100 µM; as a ZnSO4*7H20) on the mRNA relative expression of selected Zn transporters (ZnT1, ZnT5, ZnT7, ZIP6, ZIP7, ZIP10, ZIP14), in myoblast (C2C12) cells cultured in normal (10 mM) and high glucose (30 mM), and in the absence or presence of insulin (1 nM), and interleukin-6 (IL-6; 5 nM) for 24 h. The main findings of our study were that in high glucose conditions in absence of insulin or IL-6, additional Zn increased ZnT1 and ZIP6, and decreased ZnT5 and ZIP7 expressions. However, this situation is modified by insulin, where incremental Zn induced increased expressions of ZnT1, ZnT5, and all the ZIP transporters studied. In high glucose conditions and in the presence of IL-6, additional Zn caused increased expressions of ZnT7, ZIP7, and ZIP14, compared with results in the absence of IL-6. This study provides preliminary evidence for the differential expression of selected Zn transporters in C2C12 cells subjected to high glucose and incremental Zn, suggesting that important changes in intracellular Zn distribution take place in response to inflammatory and high-insulin environments. Further study is necessary to understand the implications of these findings.

Meal timing across the day modulates daily energy intake in adult patients with type 2 diabetes.

BACKGROUND/OBJECTIVES: We assessed the association between the timing of meals across the day with diet composition and metabolic parameters in patients with type-2 diabetes (T2D). SUBJECTS/METHODS: Eighty adults (55.2 ± 6.8 years, 45% males) patients with T2D (without insulin therapy) were included. Three non-consecutive dietary records assessed food intake. The onset time of each consumed meal/beverage was identified and assigned to one of three periods of the day: Period 1 (P1, 06:00-11:59 h), Period 2 (P2, 12:00-17:59 h), and Period 3 (P3, 18:00-00:30 h). RESULTS: Energy intake in P1 was lower compared to P2 and P3 (22.8 ± 7.9%, 37.5 ± 9.6%, and 39.7 ± 9.9%, respectively, P < 0.001). The same pattern was found for both total protein and fat intake, but carbohydrate intake was similar among periods. Patients with greater daily energy intake (as % of total energy) in P3 showed increased total food consumption, total energy, protein, and fat intake (all P < 0.05). The opposite pattern was observed in patients with greater daily energy intake in P1 (all P < 0.05). Regression analysis showed that daily energy intake was significantly reduced when a higher proportion of carbohydrates was eaten in P1 (vs. P3, P < 0.04). CONCLUSION: Increased energy intake late during the day is related to increased total food and daily energy intake in patients with T2D. A greater proportion of total carbohydrates eaten early during the day relates to lower total energy intake. Our results suggest that earlier food intake may be a nutritional tool for dietary and metabolic control in these patients.

Assessing the Enzymatic Hydrolysis of Salmon Frame Proteins through Different By-Product/Water Ratios and pH Regimes.

The enzymatic hydrolysis of fish by-product proteins is traditionally carried out by mixing ground by-products with water. In addition, pH control is used to avoid pH drops. Higher costs are involved due to the use of pH control systems and the consequent energy cost in the drying stage. This work aimed to evaluate the effect of these conditions on the hydrolysis of salmon frame (SF) proteins, including the SF hydrolysis without added water. SF hydrolysis by subtilisin at 50, 75, and 100% SF under different pH regimes were evaluated by released α-amino (α-NH) groups, total nitrogen, degree of hydrolysis, and estimated peptide chain length (PCL) at 55 °C. The concentration of released α-NH groups was higher in the conditions with less added water. However, the nitrogen recovery decreased from 50 to 24% at 50 and 100% SF, respectively. Changing the SF/water ratio had a more significant effect than changing the pH regime. Estimated PCL changed from 5-7 to 7-9 at 50 and 100% SF, respectively. The operating conditions affected the hydrolysis performance and the molecular characteristics of the hydrolysate.

Zinc absorption and zinc status are reduced after either sleeve gastrectomy or Roux-en-Y gastric bypass in premenopausal women with severe obesity studied prospectively over 24 postoperative months.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is known to reduce zinc absorption; the effects of vertical sleeve gastrectomy (SG) and its long-term implications on zinc absorption have not yet been studied. OBJECTIVE: The aim was to evaluate the effects of SG and RYGBP on zinc absorption and zinc status in premenopausal women with severe obesity up to 24 mo after surgery. METHODS: Twenty-six premenopausal women undergoing SG [BMI (in kg/m2): 37.3 ± 3.2] and 32 undergoing RYGBP (BMI: 42.0 ± 4.2) were studied. A series of anthropometric, dietary, and zinc status parameters (plasma and hair zinc), and the size of the exchangeable zinc pool (EZP), as well as percentage zinc absorption from a standardized dose using a stable isotope methodology were evaluated in the patients before the surgical procedure and at 12 and 24 mo after SG or RYGBP. SG patients received 15 mg and RYGBP received 25 mg of supplemental Zn/d. RESULTS: In premenopausal women, zinc absorption was decreased by 71.9% and 52.0% in SG and RYGBP, respectively, 24 mo postsurgery, compared with initial values. According to 2-factor repeated-measures ANOVA, time effect was significant (P = <0.0001), but not time × group interaction (P = 0.470). Plasma zinc below the cutoff point of 70 µg/dL increased from 0 to 15.4% and 38.1% in SG and RYGBP, respectively. Mean EZP was significantly reduced 24 mo after surgery, although no time × group interactions were observed. Hair zinc did not change across time or between groups. CONCLUSIONS: Both SG and RYGBP have profound effects on zinc absorption capacity, which are not compensated for after 24 mo. Although zinc absorption reduction was similar in both types of surgeries, plasma zinc was more affected in RYGBP than SG, despite greater zinc supplementation in RYGBP.This trial was registered at http://www.isrctn.com as ISRCTN31937503.

Zinc Supplementation and Strength Exercise in Rats with Type 2 Diabetes: Akt and PTP1B Phosphorylation in Nonalcoholic Fatty Liver.

Type 2 diabetes mellitus (T2D) is a metabolic disorder caused by chronic hyperglycemia due to a deficiency in the secretion and/or action of insulin. Zinc (Zn) supplementation and strength exercise increases insulin signaling. We evaluate the effect of Zn supplementation and strength exercise on insulin resistance in the liver of rats with diet-induced T2D through the study of phosphorylation of Akt and protein tyrosine phosphatase 1B (PTP1B). Rats were fed with a high-fat diet (HFD) for 18 weeks to induce T2D and then assigned in four experimental groups: HFD, HFD-Zn (Zn), HFD-strength exercise (Ex), and HFD-Zn/strength exercise (ZnEx) and treated during 12 weeks. Serum Zn, lipid profile, transaminases, glucose, and insulin were measured. In the liver with/without insulin stimuli, total and phosphorylated Akt (pAktSer473) and PTP1B (pPTP1BSer50) were determined by western blot. Hepatic steatosis was evaluated by histological staining with red oil and intrahepatic triglyceride (IHTG) content. There were no differences in biochemical and body-related variables. The ZnEx group showed a higher level of pAkt, both with/without insulin. The ZnEx group also showed higher levels of pPTP1B with respect to HFD and Zn groups. The ZnEx group had higher levels of pPTP1B than groups treated with insulin. Liver histology showed a better integrity and less IHTG in Ex and ZnEx with respect to the HFD group. The Ex and ZnEx groups had lower IHTG with respect to the HFD group. Our results showed that Zn supplementation and strength exercise together improved insulin signaling and attenuated nonalcoholic liver disease in a T2D rat model.

Zinc Modulates the Response to Apoptosis in an In Vitro Model with High Glucose and Inflammatory Stimuli in C2C12 Cells.

Apoptosis is programmed cell death and its alteration is related to cancer, neurologic, autoimmune, and chronic diseases. A number of factors can affect this process. The aim of this paper is to study the effect of supplemental zinc on apoptosis-related genes in C2C12 myoblast cells after being challenged with a series of stimuli, such as high glucose, insulin, and an inflammatory agent. C2C12 myoblast cells were cultured for 24 h with zinc (Zn) (ZnSO4) 10 or 100 µM and/or glucose 10 or 30 mM. In addition to these stimuli, the cells were challenged with insulin 1 nM or interleukin-6 (IL-6) 5 nM. The mRNA expression of proapoptotic genes caspase 3 and Fas, the antiapoptotic genes, Xiap and Bcl-xL and the ratio of pro-/antiapoptotic genes Bax/Bcl-2, were determined by qRT-PCR. The expression of caspase-3 gene was significantly increased in the presence of the combination high Zn/high glucose with and without the presence of insulin and IL6 in the culture medium Fas expression instead, showed uneven responses. The expression of Bcl-xL and Xiap was increased in most conditions by having high Zn in the medium regardless of the presence of insulin or IL6. Bax/Bcl2 ratio was decreased in the presence of high Zn. Zn was able to stimulate the expression of antiapoptotic genes. This effect was specially noted in high-glucose conditions with and without the presence of insulin. This effect is partially overridden by the presence of an inflammatory agent such as IL-6.

La suplementación con zinc reduce la concentración de ácidos grasos libres en pacientes con diabetes tipo 2

RESUMEN Elevadas concentraciones de ácidos grasos libres (AGL) han sido asociadas con la patogénesis de resistencia a la insulina y diabetes tipo 2 (DT2), por lo que la regulación de la lipólisis resulta prioritaria en estos pacientes. El zinc mediante sus acciones insulinomiméticas e inducción de fosfodiesterasas podría regular la liberación de AGL desde el tejido adiposo. El objetivo de esta investigación fue evaluar en pacientes con DT2 el efecto de 24 meses de suplementación con zinc sobre las concentraciones séricas de AGL en ayuno. Para este propósito: se realizó la determinación de AGL en ayuno por colorimetría enzimática, zinc plasmático por espectrofotometría de absorción atómica, y parámetros bioquímicos y antropométricos de interés en 60 pacientes con DT2 que fueron asignados aleatoriamente para recibir suplementación con 30 mg/día de zinc (n= 30) o placebo (n= 30) por 24 meses. El grupo zinc presentó menor concentración sérica de AGL al mes 24 (p = 0,034). El cambio en el índice de masa corporal, el sexo y la suplementación con zinc contribuyeron significativamente como predictores de la concentración sérica de AGL al mes 24 (R= 0,493, R2= 0,243, p= 0,001). Conclusión: la suplementación con 30 mg/día de zinc en pacientes con DT2 tuvo un efecto significativo en reducir la concentración sérica de AGL en ayuno tras 24 meses de tratamiento. Estos resultados apoyan los beneficios del zinc como coadyuvante en el tratamiento de DT2.

ABSTRACT High concentrations of free fatty acids (FFA) have been associated with the pathogenesis of insulin resistance and type 2 diabetes (T2D), making lipolysis regulation a priority in these patients. Through its insulin-mimetic actions and phosphodiesterase induction, zinc could regulate FFA release from adipose tissue. The objective of this research was to evaluate the effect of 24 months of zinc supplementation on fasting serum FFA concentrations in patients with T2D. For this purpose: fasting FFA by enzymatic colorimetric, plasma zinc by atomic absorption spectrophotometry, and biochemical and anthropometric parameter of interest were determined in 60 T2D patients who were randomly assigned to 30 mg/day of zinc supplementation (n= 30) or placebo (n= 30) for 24 months. The zinc group had lower serum FFA concentration at month 24 (p= 0.034). Body mass index change, gender, and zinc supplementation contributed significantly as predictors of serum FFA concentration at month 24 (R= 0.493, R2= 0.243, p= 0.001). Conclusion: Supplementation with 30 mg/day of zinc in patients with T2D had a significant effect in reducing serum fasting FFA concentration after 24 months of treatment. These results support the benefits of zinc as coadjutant in T2D treatment.

Fatty acid desaturation in red blood cell membranes of patients with type 2 diabetes is improved by zinc supplementation.

BACKGROUND/OBJECTIVE: Membrane flexibility can be a determining factor in pathophysiological mechanisms of type 2 diabetes (T2D). As a cofactor of delta-5 desaturase (D5D) and delta-6 desaturase (D6D), and gene expression regulator, zinc may play a role modulating membrane flexibility by increasing membrane polyunsaturated fatty acids (PUFA) abundance. The objective of this study was to evaluate the effect of a 24-month zinc supplementation (30 mg elemental zinc) on membrane fatty acid composition in patients with T2D. SUBJECTS/METHODS: Sixty patients with T2D were evaluated. Thirty were randomly assigned to the zinc supplemented group and thirty to the placebo group. Fatty acid composition in red blood cell (RBC) membranes was determined by gas chromatography. Expression of gene encoding for D5D (FADS1), and D6D (FADS2) were evaluated in peripheral blood mononuclear cells by real-time polymerase chain reaction. RESULTS: After 24 months of supplementation, a greater abundance of docosapentaenoic acid (C22:5 n-3), arachidonic acid (C20:4 n-6), adrenic acid (C22:4 n-6), and total n-6 PUFA was found (p = 0.001, p = 0.007, p = 0.033, p = 0.048, respectively). The unsaturated fatty acids/saturated fatty acids ratio, and unsaturation index was increased in the zinc supplemented group at month 24 (p = 0.003 and p  = 0.000, respectively). FADS1 gene was upregulated in the zinc group in relation to placebo at month 12 (p = 0.020). CONCLUSIONS: Supplementation with 30 mg/d elemental zinc during 24 months in patients with T2D had an effect on the composition of RBC membranes increasing PUFA abundance and in turn, improving membrane flexibility. This effect may be mediated by induction of D5D gene expression.

Nutritional Effects of Zinc on Metabolic Syndrome and Type 2 Diabetes: Mechanisms and Main Findings in Human Studies.

Zinc (Zn) plays crucial roles in mammalian metabolism. There is increasing interest about the potential beneficial effects of Zn on the prevention or treatment of non-communicable diseases. This review critically analyzes the information related to the role of Zn on the metabolic syndrome (MetS) as well as type 2 diabetes (T2D), and summarizes the biological basis of these potential effects of Zn. There are several mechanisms by which Zn may help to prevent the development or progression of MetS and T2D, respectively. Zn is involved in both insulin secretion and action in peripheral tissues. Specifically, Zn has insulin-mimetic properties that increase the activity of the insulin signaling pathway. Zn modulates long-chain polyunsaturated fatty acids levels through its action on the absorption of essential fatty acids in the intestine and its subsequent desaturation. Zn is also involved in both the assembly of chylomicrons and lipoproteins as well as their clearance, and thus, plays a role in lipolysis regulation. Finally, Zn has been found to play a role in redox metabolism, and in turn, on blood pressure. The evidence related to the association between Zn status and occurrence of MetS is inconsistent. Although there are several studies reporting an inverse relationship between Zn status or dietary Zn intake and MetS prevalence, others found a direct relationship between Zn status and MetS prevalence. Intervention studies also provide confusing information about this issue, making it hard to reach firm conclusions. Zn as part of the treatment for patients with T2D has been shown to have positive responses in terms of glucose control outcomes, but only among those with Zn deficiency.

Calcium absorption may be affected after either sleeve gastrectomy or Roux-en-Y gastric bypass in premenopausal women: a 2-y prospective study.

Background: Although Roux-en-Y gastric bypass (RYGBP) is known to reduce calcium absorption (CA), the effects of vertical sleeve gastrectomy (SG) and its long-term implications on CA have not yet been studied. Objective: The aim of this study was to evaluate changes in CA and its relation with modifications of bone mineral density (BMD), intakes of calcium and vitamin D, vitamin D status, and parathyroid hormone (PTH) concentrations ≤24 mo after SG and RYGBP, respectively. Design: Twenty-six premenopausal women undergoing SG [mean ± SD body mass index (BMI; kg/m2): 37.3 ± 3.2; age: 34.2 ± 10.2 y] and 32 undergoing RYGBP (BMI: 42.0 ± 4.2; age: 37.3 ± 8.1 y) were studied at baseline (presurgery) and followed up at 12 and 24 mo after surgery. BMD, bone alkaline phosphatase activity, and serum PTH, 25-hydroxyvitamin D [25(OH)D], calcium, magnesium, and phosphorus concentrations were determined. Food and supplement intakes were recorded. CA was measured by using a dual stable isotope method. Results: In premenopausal women, CA was significantly reduced from 36.5% ± 2.0% preoperatively to 21.0% ± 2.3% and 18.8% ± 3.4% at 12 and 24 mo post-SG surgery, respectively. CA also decreased significantly from 41.5% ± 2.8% preoperatively to 27.9% ± 3.8% and 18.5% ± 2.2% 12 and 24 mo after RYGBP, respectively. No difference was found between type of surgery (time × group interaction, P = 0.60). Considering both groups combined, 56.6% of the variance in CA at the 12-mo but not at the 24-mo follow-up was explained by serum PTH and 25(OH)D concentrations, together with vitamin D and calcium intakes. Conclusions: CA was similarly reduced in both SG and RYGBP compared with baseline, and it was not associated with changes in BMD or body weight loss. This reduction in CA could be explained only partially by calcium intake increase. This trial is registered at http://www.isrctn.com as ISRCTN31937503.

Association between zinc nutritional status and glycemic control in individuals with well-controlled type-2 diabetes.

BACKGROUND/OBJECTIVE: Interest in healthy properties of food and nutrients as co-adjuvant in type-2 diabetes therapy has increased in recent years. Zinc supplementation trials have shown improvements in glycemic control in these patients, although it seems dependent on zinc status of the individuals. The objective of this study was to evaluate the relationship between zinc nutritional status and glucose homeostasis in patients with type-2 diabetes. SUBJECTS/METHODS: Eighty patients with well controlled type-2 diabetes were recruited and clinical, anthropometric and dietary evaluations were performed. One week after, insulin sensitivity and beta cell function were assessed by a modified Frequently Sampled Intravenous Glucose Tolerance Test. Zinc status was assessed by plasma zinc and the size of rapidly Exchangeable Zinc Pool (EZP); zinc intake was also determined. Glucagon concentration was evaluated in a subsample of 36 patients. RESULTS: Patients presented a normal zinc status although zinc intake was lower than recommended. Overall, no associations were observed between zinc status and glycemic control markers. Nevertheless, positive correlations were observed between EZP and fasting insulin concentration (ρ = 0.393, p = 0.021) and HOMA-IR (ρ = 0.386, p = 0.024) in women, and between plasma zinc concentration and HbA1c (ρ = 0.342, p = 0.020) in men. CONCLUSIONS: No significant associations were found between zinc status and glycemic control parameters in patients with well-controlled type 2 diabetes and normal zinc status, although low-degree gender-dependent associations were observed. Further research is required to assess the role of zinc status in zinc deficient patients.

Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes.

Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secretion. Zinc supplementation improves blood glucose control in patients with type 2 diabetes, although there is little information about how zinc supplementation may affect glucagon secretion. The objective of this study was to evaluate the effect of 1-year zinc supplementation on fasting plasma glucagon concentration and in response to intravenous glucose and insulin infusion in patients with type 2 diabetes. A cross-sectional study was performed after 1-year of intervention with 30 mg/day zinc supplementation or a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and biochemical parameters were determined. Fasting plasma glucagon and in response to intravenous glucose and insulin infusion were evaluated. Patients of both placebo and supplemented groups presented a well control of diabetes, with mean values of fasting blood glucose and glycated hemoglobin within the therapeutic goals established by ADA. No significant differences were observed in plasma glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting, after glucose or after insulin infusions between placebo and supplemented groups. No significant effects of glucose or insulin infusions were observed on plasma glucagon concentration. One-year zinc supplementation did not affect fasting plasma glucagon nor response to intravenous glucose or insulin infusion in well-controlled type 2 diabetes patients with an adequate zinc status.

Does Zinc Really "Metal" with Diabetes? The Epidemiologic Evidence.

Zinc (Zn) is important in a number of processes related to insulin secretion and insulin activity in peripheral tissues, making this element an interesting potential co-adjuvant in the treatment of patients with type 2 diabetes (T2D). This issue has been matter of interest in recent years. The available evidence is analyzed in this review. Information from epidemiologic studies evaluating the relationship between Zn and T2D is inconsistent. Furthermore, few studies examined the association between Zn status and insulin action and/or glucose homeostasis. In terms of usefulness of Zn as a preventive agent for T2D development, information is insufficient to reach firm conclusions. Results from Zn supplementation trials found some positive effects only in those with initial sub normal Zn status in a significant proportion of individuals. In conclusion, the effect of Zn on patients with type 2 diabetes is still an open question, and better study designs are needed to clarify the real impact and characteristics of the Zn-diabetes interaction.

Micronutrient Deficiencies in Morbidly Obese Women Prior to Bariatric Surgery.

BACKGROUND: Although morbid obesity is related to excess of energy and macronutrient intake, it does not rule out the presence of micronutrient deficiencies. The aim of this study was to evaluate food intake and the prevalence of micronutrient deficiencies in a group of morbidly obese women seeking bariatric surgery. METHODS: A total of 103 morbidly obese women were studied prior to bariatric surgery. Anthropometry and body composition (dual-energy X-ray absorptiometry, DEXA) were performed on all subjects. Energy and nutrient intake was determined by food frequency questionnaire. Blood tests to assess micronutrients status, including plasma iron, ferritin, transferrin, zinc, copper, calcium, phosphorus, hemoglobin, hematocrit, mean corpuscular volume (MCV), and hair zinc, were performed. Folic acid, vitamin B12, vitamin D, and parathyroid hormone (PTH) were also assessed in 66 subjects. RESULTS: Mean energy intake was 2801 ± 970 kcal/day. Carbohydrate, protein, and lipid intake represented 55 ± 9.1, 13.9 ± 3.3, and 32.5 ± 8.2% of total energy intake, respectively. Iron, calcium, and vitamin D intake was below the recommended dietary allowance. The prevalence of nutritional deficiencies were as follows: plasma iron 12.6%, ferritin 8.7%, transferrin 14.6%, plasma zinc 2.9%, calcium 3.3%, phosphorus 2.3%, hemoglobin 7.7%, hematocrit 13.6%, MCV 6.8%, and hair zinc 15.7%. In the subsample, 10.6% had a vitamin B12 deficiency, 71.7% showed low concentrations of vitamin D, and 66% had high PTH levels. No folic acid or copper deficiencies were detected. CONCLUSIONS: Despite high daily energy intake and adequate macronutrient distribution, morbidly obese Chilean women seeking bariatric surgery present with deficient intake of some micronutrients and a high prevalence of micronutrient deficiencies.

Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is characterized by liver steatosis, oxidative stress, and drastic depletion of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), namely, eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA), which trigger lipolysis stimulation and lipogenesis inhibition. Extra virgin olive oil (EVOO) has important antioxidant effects. This study evaluated the anti-steatotic effects of n-3 LCPUFA plus EVOO in the liver of male C57BL/6J mice subjected to a control diet (CD) (10% fat, 20% protein, 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, 20% carbohydrate), without and with supplementation with n-3 LCPUFA (100 mg per kg per day) plus EVOO (100 mg per kg per day) for 12 weeks. HFD induced (i) liver steatosis (increased total fat, triacylglycerols, and free fatty acid total contents), (ii) higher fasting serum glucose and insulin levels and HOMA index, total cholesterol, triacylglycerols and TNF-α and IL-6, (iii) liver and plasma oxidative stress enhancement, (iv) depletion of the n-3 LCPUFA hepatic content, and (v) increment in lipogenic enzyme activity and reduction in lipolytic enzyme activity. These changes were either reduced (p < 0.05) or normalized to control the values in animals subjected to HFD supplemented with n-3 LCPUFA plus EVOO. In conclusion, n-3 LCPUFA plus EVOO intervention exerts anti-steatotic effects underlying antioxidant and anti-inflammatory responses, improved insulin sensitivity, and recovery of the lipolytic/lipogenic status of the liver altered by HFD, and supports the potential therapeutic use of n-3 LCPUFA plus EVOO supplementation in the treatment of human liver steatosis induced by nutritional factors or other etiologies.

Changes in bone mineral density after sleeve gastrectomy or gastric bypass: relationships with variations in vitamin D, ghrelin, and adiponectin levels.

BACKGROUND: A major long-term concern after gastric bypass (GBP) is the risk of osteoporosis; however, little is known about this complication in patients undergoing sleeve gastrectomy (SG). OBJECTIVE: To evaluate changes in bone mineral density (BMD) after GBP and SG, and its relationship with changes in vitamin D, parathyroid hormone (PTH), ghrelin, and adiponectin. METHODS: Twenty-three women undergoing GBP (BMI 42.0 ± 4.2 kg/m2; 37.3 ± 8.1 years) and 20 undergoing SG (BMI 37.3 ± 3.2 kg/m2; 34.2 ± 10.2 years) were studied before and 6 and 12 months after surgery. BMD was measured by dual-energy X-ray absorptiometry. Plasma PTH, 25-hydroxyvitamin D (25-OHD), ghrelin, and adiponectin concentrations were determined. Food as well as calcium and vitamin D supplement intake was recorded. RESULTS: Excess weight loss (mean ± SE), adjusted by baseline excess weight, was 79.1±3.8% and 74.9 ± 4.1% 1 year after GBP and SG, respectively (p = 0.481). Significant reduction in BMD for total body (TB), lumbar spine (LS), and femoral neck (FN) was observed after GBP. In the SG group, reduction in BMD was significant only for TB. Adjusted by baseline BMD, the difference between change in BMD for GBP vs. SG was not significant for TB, LS, or FN. Percent reduction in ghrelin concentration was a main factor related to total BMD loss (GBP group) and LS BMD loss (GBP and SG groups). CONCLUSIONS: One year after gastric bypass, bone mineral density was significantly affected, mainly at the femoral neck. Decreases in bone mineral density were more dramatic among patients who had greater baseline BMD and greater reduction in ghrelin concentrations.

Zinc as a potential coadjuvant in therapy for type 2 diabetes.

BACKGROUND: Type 2 diabetes is highly prevalent in populations having high rates of overweight and obesity. It is a chronic condition responsible for long-term severe dysfunction of several organs, including the kidneys, heart, blood vessels, and eyes. Although there are a number of pharmacologic products in the market to treat insulin resistance and impaired insulin secretion--the most prominent features of this disease--interventions directed at preserving the integrity and function of beta-cells in the long term are less available. The use of some nutrients with important cellular protective roles that may lead to a preservation of beta-cells has not been fully tested; among these, zinc may be an interesting candidate. OBJECTIVE: To assess the potential of zinc supplementation as coadjuvant to diabetes therapy. METHODS: This article reviews the available information on the use of zinc as part of diabetes therapy. RESULTS: Cellular and animal models provide information on the insulin mimetic action of zinc, as well as its role as a regulator of oxidative stress, inflammation, apoptosis, and insulin secretion. Zinc supplementation studies in humans are limited, although some positive effects have been reported; mainly, a modest but significant reduction in fasting glucose and a trend to decreased glycated hemoglobin (HbA1c). CONCLUSIONS: Zinc supplementation may have beneficial effects on glycemic control. Nevertheless, among the studies considered, the vast majority lasted for 6 months or less, suggesting the importance of conducting long-duration studies given the characteristics of type 2 diabetes as a chronic disease.

Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy and Roux-en-Y gastric bypass in morbidly obese women.

BACKGROUND: The effect of bariatric surgery on iron absorption is only partially known. OBJECTIVE: The objective was to study the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption and iron status. DESIGN: Fifty-eight menstruating women were enrolled in this prospective study [mean (±SD) age: 35.9 ± 9.1 y; weight: 101.7 ± 13.5 kg; BMI (in kg/m²): 39.9 ± 4.4]. Anthropometric, body-composition, dietary, and hematologic indexes and heme- and nonheme-iron absorption-using a standardized meal containing 3 mg Fe-were determined before and 12 mo after surgery. Forty-three subjects completed the 12-mo follow-up. Iron supplements were strictly controlled. RESULTS: Heme-iron absorption was 23.9% before and 6.2% 12 mo after surgery (P < 0.0001). Nonheme-iron absorption decreased from 11.1% to 4.7% (P < 0.0001). No differences were observed by type of surgery. Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG group and 63.2 ± 21.1 mg/d in the RYGBP group (P < 0.001). Serum ferritin and total-body iron decreased more after RYGBP than after SG. CONCLUSIONS: Iron (heme and nonheme) absorption is markedly reduced after SG and RYGBP. The magnitude of the decrease in heme-iron absorption is greater than that of nonheme iron. The amounts suggested as iron supplements may need to be increased to effectively prevent iron-status impairment.

Acute inhibition of iron bioavailability by zinc: studies in humans.

Iron (Fe) and zinc (Zn) deficiencies constitute two of the most important nutritional and public health problems affecting developing countries. Combined supplementation or fortification with Zn and Fe are strategies that can be used to improve the Zn and Fe status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to DMT1 and Zip14 transporter. Studies performed in humans have shown an inhibitory effect of Zn on Fe absorption when both minerals are given together as a solution in fasting conditions. We found that at low doses of iron (0.5 mg) the threshold for the inhibition of iron bioavailability was at a Zn:Fe wt/wt ratio ≥5.9:1, whereas at higher doses of Fe (10 mg) this inhibition occurred at 1:1 Zn:Fe wt/wt ratio. This differential response could be explained by the variation in the abundance of both cations as they compete for a limited number of shared transporters at the enterocyte. Conflicting results have been obtained when this interaction was studied in different food matrices. A negative interaction was not observed when Fe and Zn were provided in a composite hamburger meal, premature formula, human milk, or cow milk. A decrease on Fe absorption was observed in only 1 of 3 studies when Fe and Zn were supplied in wheat flour. The possibility of a negative interaction should be considered for supplementation or fortification programs with both microminerals.