Hana Koutníková

Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems and the heart. A gene, X25, was identified in the critical region for the FRDA locus on chromosome 9q13. This gene encodes a 210-amino acid protein, frataxin, that has homologs in distant species such as Caenorhabditis elegans and yeast. A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.

Objective To systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease. Design Systematic review and meta-analysis. Data sources Medline, EMBASE and COCHRANE from 1990 to June 2018. Eligibility criteria Randomised controlled trials (≥14 days) excluding hypercholesterolaemia, alcoholic liver disease, polycystic ovary syndrome and children <3 years. Results One hundred and five articles met inclusion criteria, representing 6826 subjects. In overweight but not obese subjects, probiotics induced improvements in: body weight (k=25 trials, d=−0.94 kg mean difference, 95% CI −1.17 to −0.70, I²=0.0%), body mass index (k=32, d=−0.55 kg/m², 95% CI −0.86 to −0.23, I²=91.9%), waist circumference (k=13, d=−1.31 cm, 95% CI −1.79 to −0.83, I²=14.5%), body fat mass (k=11, d=−0.96 kg, 95% CI −1.21 to −0.71, I²=0.0%) and visceral adipose tissue mass (k=5, d=−6.30 cm², 95% CI −9.05 to −3.56, I²=0.0%). In type 2 diabetics, probiotics reduced fasting glucose (k=19, d=−0.66 mmol/L, 95% CI −1.00 to −0.31, I²=27.7%), glycated haemoglobin (k=13, d=−0.28 pp, 95% CI −0.46 to −0.11, I²=54.1%), insulin (k=13, d=−1.66 mU/L, 95% CI −2.70 to −0.61, I²=37.8%) and homeostatic model of insulin resistance (k=10, d=−1.05 pp, 95% CI −1.48 to −0.61, I²=18.2%). In subjects with fatty liver diseases, probiotics reduced alanine (k=12, d=−10.2 U/L, 95% CI −14.3 to −6.0, I²=93.50%) and aspartate aminotransferases (k=10, d=−9.9 U/L, 95% CI −14.1 to -5.8, I²=96.1%). These improvements were mostly observed with bifidobacteria ( Bifidobacterium breve , B. longum ), Streptococcus salivarius subsp . thermophilus and lactobacilli ( Lactobacillus acidophilus , L. casei , L. delbrueckii ) containing mixtures and influenced by trials conducted in one country. Conclusions The intake of probiotics resulted in minor but consistent improvements in several metabolic risk factors in subjects with metabolic diseases. Trial registration number CRD42016033273.

In a systematic search for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) target genes, we identified S3-12 and perilipin as novel direct PPAR-gamma target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-gamma in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-gamma therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-gamma activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.