Increased Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1 Pandemic Vaccination Campaign in Finland

Peer reviewe

Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9±0.4 vs. 2.8±1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p<0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p<0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.peerReviewe

Serum metabolic profiles in overweight and obese women with and without metabolic syndrome

Objective: To identify serum biomarkers through metabolomics approach that distinguishes physically inactive overweight/obese women with metabolic syndrome from those who are metabolically healthy, independent of body weight and fat mass. Methods: We applied nuclear magnetic resonance spectroscopy-based profiling of fasting serum samples to examine the metabolic differences between 78 previously physically inactive, body weight and fat mass matched overweight/obese premenopausal women with and without MetS. MetS was defined as the presence of at least three of the following five criteria: waist circumference ≥ 88 cm, serum triacylglycerol ≥ 1.7 mmol/L, and high density lipoprotein cholesterol (HDL-C) <1.30 mmol/L, blood pressure ≥ 130/85 mmHg and fasting glucose ≥ 5.6 mmol/L). Principal component analysis was used to reduce the large number of correlated variables to fewer uncorrelated factors. Results: Two metabolic factors were associated with MetS independent of BMI, fat mass, waist circumference and physical activity/fitness. Factor comprising branched-chain amino acids (BCAA) and aromatic amino acids (AAA) and orosomucoid was associated with all clinical risk factors (p < 0.01 for all). Conclusion: Two metabolic factors distinguish overweight/obese women with metabolic syndrome from those who are metabolically healthy independent of body weight, fat mass and physical activity/fitness. In particular, factor comprising BCAA, AAA and orosomucoid seems auspicious biomarker determining metabolic health as it was associated with all clinical risk factors. Further research is needed to determine the public health and clinical significance of these results in terms of screening to identify those at greatest cardio-metabolic risk for whom appropriate intervention strategies should be developed.peerReviewe

Mean metabolite component levels stratified by the healthy control and NAFLD groups (MIXED model estimated marginal means with 95% confidence intervals are given taking into account shared environment within family, and contrast estimates’ p-values were used to localize the significant differences between the two groups and group by gender interaction).

<p>NAFLD = non-alcohol fatty liver disease; values are given as mean and 95% confident interval (CI). Factor 1 (Omega 7 and 9 and saturated fatty acids, total fatty acids, mono-unsaturated fatty acids); Factor 2 (isoleucine, leucine, valine, phenylalanine, tyrosine and orosomucoid); Factor 3 (acetate, alanine, lactate, pyruvate); Factor 4 (esterified cholesterol, free cholesterol, omega 6 fatty acids, phosphoglycerides, phosphocholines and sphingomyelines); Factor 5 (beta-hydroxybutyrate, citrate, histidine); Factor 6 (acetoacetate, glutamine)</p><p>Mean metabolite component levels stratified by the healthy control and NAFLD groups (MIXED model estimated marginal means with 95% confidence intervals are given taking into account shared environment within family, and contrast estimates’ p-values were used to localize the significant differences between the two groups and group by gender interaction).</p

Physical characteristics, fat mass distribution, glucose metabolism hormones and liver enzymes in the healthy controls and NAFLD group (MIXED model estimated marginal means with 95% confidence intervals are given taking into account shared environment within family (husband and wife) and contrast estimates’ p-values were used to localize the significant differences between the two groups and group by gender interaction).

<p>NAFLD = non-alcohol fatty liver disease; BMI = body mass index; FM = fat mass of the whole body; SAT = abdominal subcutaneous adipose tissue; VAT = visceral adipose tissue; RAT = retroperitoneal adipose tissue; IMCL = intra-myocellular lipids; EMCL = extra-myocellular lipids; E = energy; SAFA = saturated fatty acids; MUFA = monounsaturated fatty acids; PUFA = polyunsaturated fatty acids; Ch = carbohydrate; PA = physical activity; hsCRP = high-sensitivity C-reactive protein; NEFA = non-esterified fatty acids; TG = triglycerides; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = γ-glutamyltransferase.</p><p>Physical characteristics, fat mass distribution, glucose metabolism hormones and liver enzymes in the healthy controls and NAFLD group (MIXED model estimated marginal means with 95% confidence intervals are given taking into account shared environment within family (husband and wife) and contrast estimates’ p-values were used to localize the significant differences between the two groups and group by gender interaction).</p

Correlations between serum metabolites factor 2 (isoleucine, leucine, valine, phenylalanine, tyrosine and orosomucoid) and different adipose tissue gene expression clusters in certain pathways.

<p>Each dot represents an individual and the line is a linear regression fit line.</p

KEGG pathway enrichment analysis of differentially expressed genes in adipose tissue.

<p>Count = Amount of differentially expressed genes that mapped on pathway. Size = Total amount of genes involved in pathway.</p><p>KEGG pathway enrichment analysis of differentially expressed genes in adipose tissue.</p