The city of Yakutsk: a case of study for human brown adipose tissue in extremely cold conditions

The discovery of the presence of functional brown adipose tissue (BAT) also in healthy humans [1-3] has focused the attention of the scientific community on the possibility to expand body BAT content as a therapeutic strategy for the treatment and prevention of obesity and the associated metabolic disorders. Indeed, white-to- brown adipocyte transdifferentiation, leading to “browning” of the adipose organ, has been shown to reduce body weight and improve metabolic parameters in obese and insulin-resistant animal models. BAT from subject exposed daily to extremely cold outdoor temperatures has never been studied through morphological techniques. In this context, an exciting case of study are the citizens of Yakutsk, an East- ern Siberian population exposed to the annual average temperature of -10 °C, that peaks up to -50°C during winter. In autoptic fat biopsies from a 54-year-old patient living in Yakutsk BAT is present in the perirenal and para-aortic fat specimens. Importantly, the mean adipocyte area of the subcutaneous fat from this patient is significantly lower than the mean area of subcutaneous adipocytes obtained from age- and sex-matched Italian patients. Statistical analysis of data obtained from the Territorial Organ of the Federal State Statistics Service of the Republic of Sakha (Yakutia), the Yakut Republican Medical Information and Analytical Center of the Ministry of Health of Yakutia showed a correlation between home heating and type-2 diabetes incidence during the years from 1994 to 2013, a period in which the indoor temperature increased significantly. The nutritional values of food consumed during these years also changed in parallel with the worsening of inhabitants metabolic health conditions. Taken together these data suggest a possible link between the metabolic condi- tions of inhabitants of Yakutia and the living temperature experienced

Hematopoietic Disorders, Renal Impairment and Growth in Mucopolysaccharidosis-Plus Syndrome

Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders (LSD) characterized by the excessive accumulation of glycosaminoglycans (GAG). Conventional MPS, caused by inborn deficiencies of lysosomal enzymes involved in GAG degradation, display various multisystemic symptoms—including progressive neurological complications, ophthalmological disorders, hearing loss, gastrointestinal and hepatobiliary issues, cardiorespiratory problems, bone and joint abnormalities, dwarfism, and coarse facial features. Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease caused by a mutation in the endo-lysosomal tethering protein VPS33A, shows additional renal and hematopoietic abnormalities (“Plus symptoms”) uncommon in conventional MPS. Here, we analyze data from biochemical, histological, and physical examinations—particularly of blood counts and kidney function—to further characterize the clinical phenotype of MPSPS. A series of blood tests indicate hematopoietic symptoms including progressive anemia and thrombocytopenia, which correlate with histological observations of hypoplastic bone marrow. High urinary excretion of protein (caused by impairments in renal filtration), hypoalbuminemia, and elevated levels of creatinine, cholesterol, and uric acid indicate renal dysfunction. Histological analyses of MPSPS kidneys similarly suggest the extensive destruction of glomerular structures by foamy podocytes. Height and weight did not significantly deviate from the average, but in some cases, growth began to decline at around six months or one year of age