Microbiota Composition of Breast Milk from Women of Different Ethnicity from the Manawatu-Wanganui Region of New Zealand.

Human breastmilk components, the microbiota and immune modulatory proteins have vital roles in infant gut and immune development. In a population of breastfeeding women (n = 78) of different ethnicities (Asian, Maori and Pacific Island, New Zealand European) and their infants living in the Manawatu-Wanganui region of New Zealand, we examined the microbiota and immune modulatory proteins in the breast milk, and the fecal microbiota of mothers and infants. Breast milk and fecal samples were collected over a one-week period during the six to eight weeks postpartum. Breast milk microbiota differed between the ethnic groups. However, these differences had no influence on the infant's gut microbiota composition. Based on the body mass index (BMI) classifications, the mother's breast milk and fecal microbiota compositions were similar between normal, overweight and obese individuals, and their infant's fecal microbiota composition also did not differ. The relative abundance of bacteria belonging to the Bacteroidetes phylum was higher in feces of infants born through vaginal delivery. However, the bacterial abundance of this phylum in the mother's breast milk or feces was similar between women who delivered vaginally or by cesarean section. Several immune modulatory proteins including cytokines, growth factors, and immunoglobulin differed between the BMI and ethnicity groups. Transforming growth factor beta 1 and 2 (TGFß1, TGFß2) were present in higher concentrations in the milk from overweight mothers compared to those of normal weight. The TGFß1 and soluble cluster of differentiation 14 (sCD14) concentrations were significantly higher in the breast milk from Maori and Pacific Island women compared with women from Asian and NZ European ethnicities. This study explores the relationship between ethnicity, body mass index, mode of baby delivery and the microbiota of infants and their mothers and their potential impact on infant health.

Human Milk Composition and Dietary Intakes of Breastfeeding Women of Different Ethnicity from the Manawatu-Wanganui Region of New Zealand.

Human milk is nutrient rich, complex in its composition, and is key to a baby's health through its role in nutrition, gastrointestinal tract and immune development. Seventy-eight mothers (19⁻42 years of age) of Asian, Maori, Pacific Island, or of European ethnicity living in Manawatu-Wanganui, New Zealand (NZ) completed the study. The women provided three breast milk samples over a one-week period (6⁻8 weeks postpartum), completed a three-day food diary and provided information regarding their pregnancy and lactation experiences. The breast milk samples were analyzed for protein, fat, fatty acid profile, ash, selected minerals (calcium, magnesium, selenium, zinc), and carbohydrates. Breast milk nutrient profiles showed no significant differences between the mothers of different ethnicities in their macronutrient (protein, fat, carbohydrate, and moisture) content. The breast milk of Asian mothers contained significantly higher levels of polyunsaturated fatty acids (PUFAs), omega-3 (n-3) and omega-6 (n-6) fatty acids, docosahexaenoic acid (DHA), and linoleic acids. Arachidonic acid was significantly lower in the breast milk of Maori and Pacific Island women. Dietary intakes of protein, total energy, saturated and polyunsaturated fat, calcium, phosphorus, zinc, iodine, vitamin A equivalents, and folate differed between the ethnic groups, as well as the number of serves of dairy foods, chicken, and legumes. No strong correlations between dietary nutrients and breast milk components were found.

Mice lacking the neuropeptide alpha-calcitonin gene-related peptide are protected against diet-induced obesity.

Alpha-calcitonin gene-related peptide (alphaCGRP) is a neuropeptide that is expressed in motor and sensory neurons. It is a powerful vasodilator and has been implicated in diverse metabolic roles. However, its precise physiological function remains unclear. In this study, we investigated the role of alphaCGRP in lipid metabolism by chronically challenging alphaCGRP-specific knockout (alphaCGRP(-/-)) and control mice with high-fat diet regimens. At the start of the study, both animal groups displayed similar body weights, serum lipid markers, and insulin sensitivity. However, alphaCGRP(-/-) mice displayed higher core temperatures, increased energy expenditures, and a relative daytime (nonactive) depression in respiratory quotients, which indicated increased beta-oxidation. In response to fat feeding, alphaCGRP(-/-) mice were comparatively protected against diet-induced obesity with an attenuated body weight gain and an overall reduction in adiposity across all the three diets examined. AlphaCGRP(-/-) mice also displayed improved glucose handling and insulin sensitivity, lower im and hepatic lipid accumulation, and improved overall metabolic health. These findings define a new role for alphaCGRP as a mediator of energy metabolism and opens up therapeutic opportunities to target CGRP action in obesity.

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease.

Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial beta-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

Molecular changes evoked by triethylenetetramine treatment in the extracellular matrix of the heart and aorta in diabetic rats.

Most patients with diabetes die from cardiac or arterial disease, for which there are limited therapeutic options. Free Cu(2+) ions are strongly pro-oxidant, and chelatable-Cu(II) is increased in the diabetic heart. We reported previously that treatment by Cu(II)-selective chelation with triethylenetetramine (TETA) evokes elevated urinary Cu(II) in diabetic rats and humans in whom it also improved hallmarks of established left ventricular (LV) disease. Here, we treated diabetic rats with TETA and evaluated its ability to ameliorate Cu(2+)-mediated LV and arterial damage by modifying the expression of molecular targets that included transforming growth factor (TGF)-beta1, Smad4, extracellular matrix (ECM) proteins, extracellular superoxide dismutase (EC-SOD), and heparan sulfate (HS). Eight-weeks of TETA treatment significantly improved cardiac diastolic function but not [glucose](plasma) in diabetic animals. LV and aortic mRNAs corresponding to TGF-beta1, Smad4, collagen types I, III, and IV, and fibronectin-1, and plasminogen activator inhibitor-1, were elevated in untreated diabetic animals and normalized after TETA treatment. EC-SOD mRNA and protein, and [HS](tissue) were significantly decreased in diabetes and restored by drug treatment. Candidate molecular mechanisms by which TETA could ameliorate diabetic cardiac and arteriovascular disease include the suppression of an activated TGF-beta/Smad signaling pathway that mediates increased ECM gene expression and restoration of normal EC-SOD and HS regulation. These findings are relevant to the restoration toward normal by TETA treatment of cardiac and arterial structure and function in diabetes.