AA and DHA are Decreased in Paediatric AD/HD and Inattention is Ameliorated by Increased Plasma DHA

The purpose of this study was to assess long chain polyunsaturated fatty acid (LCPUFA) status in relation to socio-behavioral outcomes in children with Attention Deficit/Hyperactivity Disorder (AD/HD). In a case-control design, plasma phospholipid fatty acid content was assessed in children aged 5–12 years with AD/HD and in typically functioning children. Dietary intakes of LCPUFAs arachidonic acid (AA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) were quantified using a four-day food record, polymorphisms were determined in FADS1 and FADS2, and socio-behavioral outcomes were assessed using the Conners 3 Parent Rating Scales in a cross section of children with AD/HD. Compared to typically functioning children, plasma AA and DHA were 40% lower in children with AD/HD. Median intake of AA, but not DHA, was higher in children with AD/HD compared to typically functioning children. Polymorphisms in FADS1 (rs174546) and FADS2 (174575) were associated with higher plasma linoleic acid (LA; 18:2n6) level. Plasma DHA level was inversely associated with inattention score. Despite having an elevated intake of AA, children diagnosed with AD/HD have a reduction in plasma AA level which may be due in part to polymorphisms in the fatty acid desaturase (FADS) gene cluster or increased conversion to AA-derived metabolites. Increasing intake of DHA may ameliorate symptoms of inattention in AD/HD

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature of the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events, formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear. Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Development of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics

De Novo Lipogenesis and Cholesterol Synthesis in Humans with Long-Standing Type 1 Diabetes Are Comparable to Non-Diabetic Individuals

<div><p>Background</p><p>Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis.</p><p>Methods</p><p>Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry.</p><p>Results</p><p>Fasting total hepatic lipogenesis (3.91±0.90% vs. 5.30±1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60±4.90% vs. 26.66±4.57%; P = 0.76), palmitic (12.52±2.75% vs. 13.71±2.64%; P = 0.65), palmitoleic (3.86±0.91% vs. 4.80±1.22%; P = 0.65), stearic (5.55±1.04% vs. 6.96±0.97%; P = 0.29), and oleic acid (1.45±0.28% vs. 2.10±0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2±1.3% vs. 7.3±0.8%/day; P = 0.88) and CE (1.9±0.4% vs. 2.0±0.3%/day; P = 0.96) and hepatic FC (8.2±2.0% vs. 8.1±0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects.</p><p>Conclusions</p><p>Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans.</p></div

Schematic of the testing day design.

<p>Blood samples were taken at fasting (0 h) and every 2 h for 8 h after the D₂O administration and breakfast completion. A lunch meal was provided after the 4 h sample, and take-away foods were provided for the subject to consume at home during the evening, before returning the following morning for a fasting 24 h blood sample.</p

Synthesis of cholesterol determined from whole-body and hepatic free cholesterol (FC) and cholesteryl ester (CE) fractions at fasting and postprandial timepoints.

<p>Fasting FC-FSR was 7.3±0.8% in Control subjects compared to 8.3±1.2% in diabetic subjects (P = 0.65), VLDL-FC-FSR was 8.1±0.8% vs. 8.2±2.0% (P = 0.72), and CE-FSR was 2.0±0.3% vs. 1.9±0.3% (P = 0.93) (<b>A</b>). Postprandial FC-FSR (<b>B</b>) at 4 h (1.8±0.9% vs. 2.2±1.1%, P = 0.36) and 8 h (2.8±1.3% vs. 2.9±1.5%, P = 0.65) was similar between groups, as was CE-FSR (<b>C</b>) at 4 h (0.11±0.12% vs. 0.31±0.37%, P = 0.37) and 8 h (0.37±0.24% vs. 0.33±0.34%, P = 0.71). Black bars, control non-diabetic subjects; white bars, type 1 diabetic subjects; data presented as mean ± SEM.</p

Fasting hepatic de novo fatty acid synthesis (DNFA) of total and individual fatty acids, postprandial synthesis of palmitate, and VLDL-TG fatty acid composition in control and type 1 diabetic subjects.

<p><i>Panel A</i> - Fasting (24 h) total hepatic FA synthesis was similar between control and diabetic subjects (5.30±1.22% vs. 3.91±0.90%, respectively; P = 0.41), and was similar for individual FA including myristic acid (14∶0; 26.66±4.57% vs. 28.60±4.90%, P = 0.76), palmitic acid (16∶0; 13.71±2.64% vs. 12.52±2.75%, P = 0.65), palmitoleic acid (16∶1; 4.80±1.22% vs. 3.86±0.91%, P = 0.65), stearic acid (18∶0; 6.96±0.97% vs. 5.55±1.04%, P = 0.29), and oleic acid (18∶1; 2.10±0.51% vs. 1.45±0.28%, P = 0.21). <i>Panel B</i> – Similar to fasting, postprandial synthesis of palmitate, the major product of de novo lipogenesis, was not significantly different in diabetic compared to control subjects (P = 0.38). <i>Panel C</i> – Fatty acid composition of VLDL-TG was not different between groups except for 16∶0, which was significantly lower in diabetic subjects compared to controls (P = 0.015). Arrows and “meal” on Panel B indicate when a meal was fed at breakfast (time 0) and lunch (time 4 h). Black bars or circles, control non-diabetic subjects; white bars or circles, type 1 diabetic subjects; data presented as mean ± SEM.</p