Mardia López-Alarcón

The FTO gene is associated with adulthood obesity in the Mexican population.

Common polymorphisms in the fat mass and obesity‐associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican‐Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single‐nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B‐cell function (HOMA‐B), and with higher homeostasis model assessment of insulin sensitivity (HOMA‐S) only in nonobese individuals (P dom = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican‐Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.

Participation of mammary gland in long-chain polyunsaturated fatty acid synthesis during pregnancy and lactation in rats

Metabolic adaptations are triggered in the maternal organism to synthesize milk with an adequate concentration of long-chain polyunsaturated fatty acids (LC-PUFAs) required to the newborn. They may be a high uptake of dietary linoleic acid and its conversion to LC-PUFAs by desaturases of fatty acids (FADS) 1 and 2 in the mammary gland (MG). It is unknown if they also occur from onset of pregnancy. The aim of this study was to explore the participation of the MG as a mechanism involved in LC-PUFAs synthesis to support their demand during pregnancy and lactation in rats. The expression of desaturases in MG was significantly (P<0.05) higher (12.3-fold for FADS1 and 41.2-fold for FADS2) during the late pregnancy and throughout lactation (31.7-fold for FADS1 and 67.1-fold higher for FADS2) than in nonpregnant rats. SREBF-1c showed a similar pattern of increase during pregnancy but remained higher only during the early lactation (11.7-fold, P<0.005). Transcript of ELOVL6 and FASN increased throughout pregnancy and lactation, respectively. ELOVL5 mRNA increased in MG only during lactation (2.8 to 5.3-fold, P<0.005). Accordingly, a higher content of LC-PUFAs was found in lactating MG than in nonpregnant rats. Results suggest that MG participates from late pregnancy and throughout lactation by expressing desaturases and elongases as a mechanism involved in LC-PUFAs synthesis, probably by SREBF-1c. Because desaturases and ELOVL5 were expressed in cultured lactocytes and such expression was downregulated by linoleic and arachidonic acid, these cells may be a useful model for understanding the regulatory mechanisms for LC-PUFAs synthesis in MG.

Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

Effect of dietary levels of corn oil on maternal arachidonic acid synthesis and fatty acid composition in lactating rats.

OBJECTIVE We examined the effect of different amounts of dietary corn oil rich in linoleic acid (LA) on the endogenous synthesis of arachidonic acid (AA), uptake of its precursor LA, and fatty acid composition of tissues involved in the supply of long-chain polyunsaturated fatty acids for milk synthesis. METHODS Female Sprague Dawley rats received one of the following diets during pregnancy and lactation: a low-lipid diet (LLD; 2%), an adequate-lipid diet (ALD; 5%), or a high-lipid diet (HLD; 10%). Lipids were provided by corn oil. On day 12 of lactation we measured the endogenous synthesis of AA and quantified the conversion of (13)C-LA to (13)C-AA and the metabolic fate of (13)C-LA from all dietary groups. RESULTS The LLD rats demonstrated larger amounts of endogenous synthesis of (13)C-AA and more dietary (13)C-LA transferred to the mammary gland (MG) than HLD rats during lactation. The proportion of medium-chain fatty acids was higher in the MG, milk clot, and liver of LLD than of HLD rats. Daily volume and 24-h yield of lipids and energy were lower in LLD rats than in HLD rats. Measurements of milk composition demonstrated that fat concentration significantly increased as lipid concentration increased in the diet. CONCLUSION These results suggest that maternal adaptations used to compensate for diets deficient in long-chain polyunsaturated fatty acids include increased endogenous synthesis of AA and elevated uptake of LA in the MG and increased synthesis of medium-chain polyunsaturated fatty acids. It appears that the MG and liver participate together for AA synthesis for milk when this fatty acid is not provided in the diet.

Coexisting role of fasting or feeding and dietary lipids in the control of gene expression of enzymes involved in the synthesis of saturated, monounsaturated and polyunsaturated fatty acids

In the liver, maintaining lipid homeostasis is regulated by physiological and exogenous factors. These lipids are synthesized by Fasn, elongases and desaturases. Interactions in an organism among these factors are quite complex and, to date, relatively little is known about them. The aim of this study was to evaluate the coexisting role of physiological (insulin, fasting and feeding) and exogenous (dietary lipids) factors in the control of gene expression of Fasn, elongases and desaturases via Srebf-1c in liver from rats. Gene expression of encoding enzymes for fatty acid synthesis and fatty acid composition was evaluated in liver from rats in fasting and feeding (at 30, 60, 90 and 120 min after feeding) when food intake (adequate or high-lipid diet) was synchronized to a restricted period of 7h. Fasn, Scd and Fads2 were induced during 120 min after initial feeding in both dietary groups. This induction may be activated in part by insulin via Srebf-1c. Also, we showed for the first time that Elovl7 may be regulated by insulin and dietary lipids. The failure to synthesize saturated and monounsaturated fatty acids is consistent with a downregulation of Fasn and Scd, respectively, by dietary lipids. A higher content of LC-PUFAs was observed due to a high expression of Elovl2 and Elovl5, although Fads2 was suppressed by dietary lipids. Therefore, elongases may have a mechanism that is Srebf-1c-independent. This study suggests that a high-lipid diet triggers, during 120 min after initial feeding, a tight coordination among de novo lipogenesis, elongation, and desaturation and may not always be regulated by Srebf-1c. Finally, upregulation by feeding (insulin) of Fasn, Scd, Fads2 and Srebf-1c is insufficient to compensate for the inhibitory effect of dietary lipids.

Excessive Refined Carbohydrates and Scarce Micronutrients Intakes Increase Inflammatory Mediators and Insulin Resistance in Prepubertal and Pubertal Obese Children Independently of Obesity

Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient (P < 0.01). Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity.

The effect of gestational age on expression of genes involved in uptake, trafficking and synthesis of fatty acids in the rat placenta

Gestation triggers a tight coordination among maternal tissues to provide fatty acids (FA) to the fetus through placental transport; however, there is insufficient evidence regarding regulation of proteins involved in placental transport of FA according to gestational age. The aim of this study was to determine the role of gestational age on the expression of genes involved in FA uptake, trafficking and synthesis in the rat placenta to support fetal demands. Gene expression of encoding proteins for placental transport and synthesis of FA was measured in placenta. Also, FA composition was measured in placenta, fetuses and newborns. mRNA expression of lipoprotein lipase (lpl) and fatp-1 (for uptake) was 4.4- and 1.43-fold higher, respectively, during late gestation than at P14, but expression of p-fabp-pm decreased 0.37-fold at late pregnancy in comparison with P14. Only mRNA fabp-4 member for trafficking of FA was 2.95-fold higher at late gestation than at P14. mRNA of fasn and elovl-6 participating in saturated FA and enzymes for the polyunsaturated FA synthesis were downregulated during late gestation and their regulator srebf-1c increased at P16. This study suggests that gestational age has an effect on expression of some genes involved in uptake, trafficking and synthesis of FA in the rat placenta; mRNA expression of lpl and, fatp-1 for uptake and fabp-4 implicated in trafficking was expressed at high levels at late gestation. In addition, placenta expresses the mRNAs involved in FA synthesis; these genes were expressed at low levels at late gestation. Additionally, mRNAs of Srebf-1c transcriptional regulator of desaturases and elongases was highly expressed during late gestation. Finally, these changes in the rat placenta allowed the placenta to partially supply saturated and monounsaturated FA to the fetus.

Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: Updating the evidence

The use of n-3 polyunsaturated fatty acids in surgical patients has risen by the fact that this may attenuate systemic and acute inflammatory responses secondary to surgical trauma through modulation of inflammatory mediators and cell membrane interactions. Moreover, the inclusion of n-3 fatty acids in clinical trials as part of the therapy in patients, who expect to undergo a surgical stress, suggests benefits on clinical progress. Therefore, the objective of this article is to review data from n-3 polyunsaturated fatty acid effects on biochemical parameters and on reduced length of hospitalization, number of infections, and mortality as main clinical outcomes in human surgical patients.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study

Background: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. Methods: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. Results: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1β+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1β+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. Conclusions: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women.

Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue.