Probiotic interventions promote metabolic health in high fat-fed hamsters in association with gut microbiota and endocannabinoidome alterations.

Probiotics represent a promising tool to improve metabolic health, including lipid profiles and cholesterol levels. Modulation of the gut microbiome and the endocannabinoidome - two interrelated systems involved in several metabolic processes influenced by probiotics - has been proposed as a potential mechanism of action. This study establishes the impact of probiotics on metabolic health, gut microbiota composition and endocannabinoidome mediators in an animal model of hypercholesterolaemia. Syrian hamsters were fed either a low-fat low-cholesterol or high-fat high-cholesterol (HFHC) diet to induce hypercholesterolaemia and gavaged for 6 weeks with either Lactobacillus acidophilus CL1285, Lactiplantibacillus plantarum CHOL-200 or a combination of the two. Globally, probiotic interventions ameliorated, at least partially, lipid metabolism in HFHC-fed hamsters. The interventions, especially those including L. acidophilus, modified the gut microbiota composition of the small intestine and caecum in ways suggesting reversal of HFHC-induced dysbiosis. Several associations were observed between changes in gut microbiota composition and endocannabinoidome mediators following probiotic interventions and both systems were also associated with improved metabolic health parameters. For instance, potential connexions between the Eubacteriaceae and Deferribacteraceae families, levels of 2­palmitoylglycerol, 2­oleoylglycerol, 2­linoleoylglycerol or 2­eicosapentaenoylglycerol and improved lipid profiles were found. Altogether, our results suggest a potential crosstalk between gut microbiota and the endocannabinoidome in driving metabolic benefits associated with probiotics, especially those including L. acidophilus, in an animal model of hypercholesterolaemia.

Stearic acid content of abdominal adipose tissues in obese women.

OBJECTIVE: Subcutaneous (SC) adipose tissue stearic acid (18:0) content and stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have been suggested to be altered in obesity. The objective of our study was to examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level in women. SUBJECTS AND METHODS: Fatty acid content was determined by capillary gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10 women with either small or large OM adipocytes. Samples from 10 additional women were used to measure SCD1 mRNA and protein expression, total extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as insulin receptor (IR) expression levels. RESULTS: OM fat 18:0 content was significantly lower in women with large OM adipocytes compared with women who had similar adiposity, but small OM adipocytes (2.37±0.45 vs 2.75±0.30 mg per 100 g adipose tissue, respectively, P0.05). OM fat 18:0 content was negatively related to the visceral adipose tissue area (r=-0.44, P=0.05) and serum triglyceride levels (r=-0.56, P<0.05), while SC fat 18:0 content was negatively correlated with total body fat mass (BFM) (r=-0.48, P<0.05) and fasting insulin concentration (r=-0.73, P<0.005). SC adipose tissue desaturation index (18:1/18:0), SCD1 expression and protein levels were positively correlated with BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1 mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR expression. CONCLUSION: The presence of large adipocytes and increased adipose mass in a given fat compartment is related to reduced 18:0 content and increased desaturation index in women, independently of dietary fat intake. The depot-specific difference in ERK1/2 expression and activation, as well as in SCD1 and IR expression in obese women is consistent with the hypothesis that they may predominantly develop SC fat, which could in turn help protect from metabolic disorders.

Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women.

OBJECTIVES: Growth hormone (GH)-deficient individuals display increased adiposity that can be effectively reduced by GH therapy because of GH's lipolytic effects. However, similar GH treatments of individuals with idiopathic obesity (not associated with an endocrinopathy/syndrome) have had little success. We hypothesized that this form of obesity may be associated with GH resistance at the level of the adipocyte because of reduced GH receptor (GHR) expression. SUBJECTS AND METHODS: We studied GHR expression in omental and subcutaneous fat tissues from a cohort of 55 women ranging from lean to obese by various adiposity parameters. mRNA levels of total GHR and the dominant-negative truncated GHR(1-279) (trGHR) form were assayed by quantitative reverse transcriptase-PCR. Associations between adiposity measures and GHR levels as well as trGHR/GHR ratios were analyzed. RESULTS: Total GHR mRNA expression was 2-3-fold lower in omental as well as subcutaneous adipose tissues of obese compared with lean women (P ≤ 0.05-0.001). Lean individuals expressed higher GHR mRNA levels in omental fat compared with subcutaneous (P ≤ 0.01); in obese women, this depot-specific difference was lost. Omental and subcutaneous adipose GHR mRNA levels displayed significant negative correlations with a spectrum of indicators of obesity while, in subcutaneous fat, there was a significantly higher trGHR/GHR ratio with increasing adiposity (P ≤ 0.05). CONCLUSION: These results support our hypothesis that, with obesity, there is lower GHR expression in the adipocyte, and suggest one possible explanation why GH supplementation is not an effective treatment for individuals with idiopathic obesity.

Correlation between prenatal velocity waveforms in the aortic isthmus and neurodevelopmental outcome between the ages of 2 and 4 years.

OBJECTIVE: Experimental studies on fetal lambs have shown that during an increase in the resistance to placental flow the delivery of oxygen to the brain is preserved as long as net flow through the aortic isthmus is antegrade. Our purpose was to determine whether the same changes in aortic isthmus flow in human subjects have any impact on neurodevelopmental outcome. STUDY DESIGN: Forty-four fetuses were retrospectively included in this study on the basis of an abnormal Doppler velocity in the umbilical artery. Mean gestational age at delivery was 33.0 +/- 2.0 weeks and mean birth weight 1386 +/- 435 g. The neurodevelopmental condition was assessed between the ages of 2 and 4 years. The developmental score was analyzed in relation to the flow patterns in the fetal aortic isthmus, which were classified as follows: group A, net isthmic flow antegrade (defined as the ratio of the systolic antegrade to the diastolic retrograde velocity integrals) (n = 39); group B, net isthmic flow retrograde (n = 5). RESULTS: Nonoptimal neurodevelopment was observed in 19 (49%) of 39 fetuses in group A and in all 5 fetuses (100%) in group B. This difference is significant and leads to a relative risk of 2.05 (95% confidence interval, 1.49-2.83) for neurodevelopmental deficit when predominantly retrograde flow is observed in the fetal aortic isthmus before birth. CONCLUSION: Measuring the ratio of antegrade to retrograde velocity integrals in the aortic isthmus could help in the indirect assessment of cerebral oxygenation during placental circulatory insufficiency.

Sirenomelia in an identical twin: a case report.

Sirenomelia, or the mermaid syndrome, is the most extreme example of the caudal regression syndrome. It invariably presents with lower limb fusion, sacral and pelvic bony anomalies, absent external genitalia, anal imperforation, and renal agenesis or dysgenesis. Because of the resultant oligohydramnios, these infants most often have Potter's facies and pulmonary hypoplasia. There are approximately 300 cases reported in the literature, 15% of which are associated with twinning, most often monozygotic. The syndrome of caudal regression is thought to be the result of injury to the caudal mesoderm early in gestation. It has been suggested that the association of the most extreme form of caudal regression, sirenomelia, with monozygotic twinning may represent developmental arrest of the primitive streak, with creation of a second primitive streak that gives rise to the usually normal twin. The embryology of the various presentations of the caudal regression syndrome may be further delineated by studying infants with this dramatic and fatal syndrome.

Outcome at school age of children with birthweights of 1000 grams or less.

A follow-up study was done of extremely low-birthweight infants (less than or equal to 1000g) born between 1976 and 1979, a period when aggressive intervention was not routine practice. The survival rate was 19 per cent. 44 of the 46 survivors were followed to a mean age of 6 1/2 years. By five years of age 23 of the 44 children had been admitted to hospital, mainly for surgery and respiratory problems. Eight of 31 five-year-old children were growth-retarded and five of 26 were microcephalic. Among 44 children, ophthalmological problems were found in nine cases and neurosensory impairments (cerebral palsy, deafness) in seven. 12 children were mentally handicapped or had impaired intelligence (IQ or DQ less than 85). Over-all, 14 of the 44 children had impairments, severe in four cases and moderate in 10. Mean verbal IQ was significantly lower than mean performance IQ. Among 37 children in school or in remedial programs, nine required special education and another 12 in regular classes either failed or had very poor results, or needed extra professional help. Only 16 of the children had no significant problems in school. These findings indicate that extremely low birthweight (less than or equal to 1000g) represents a major risk to life, health (hospital admissions), long-term growth, neurosensory integrity, cognitive development and learning potential.

Early discharge of low birthweight infants.

A study was conducted to see if the discharge weight of preterm infants born at less than or equal to 2000 g could safely be reduced. A study group (21 infants) was discharged 'early' at a mean weight of 2010 g (1890-2190) provided there were no medical problems, weight gain was adequate, temperature control in room air was stable, all feedings were by breast, and the mother was ready to have the baby home. A control group (17 infants) was discharged at a mean weight of 2261 g (2200-2400). The duration of time in hospital for the 'early' group was shortened by 11.6 days. At expected date of delivery the weight of infants in each group was similar (3095 +/- 403 compared with 3146 +/- 453 g); length, head circumference, and haemoglobin concentration in each group were similar too. There was no morbidity or mortality in either group. Early discharge did not affect mothering confidence. This study shows that low birthweight infants can be discharged early (at 2000 +/- 100 g) provided appropriate criteria are met, home conditions are adequate, and follow-up is available.