In the last few decades, rapid changes in lifestyle have led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance, dyslipidemia, type 2 diabetes and kidney disease. The surplus of calories is normally stored as triglycerides in adipose tissue. However, excess lipids can also accumulate ectopically in other organs, including the kidney, contributing to their damage through toxic processes named lipotoxicity. The kidney is negatively affected by dyslipidemia, lipid accumulation and changes in circulating adipokines that bring about alterations in renal lipid metabolism and promote insulin resistance, generation of reactive oxygen species and endoplasmic reticulum stress, ultimately leading to alterations in the glomerular filtration barrier and renal failure. This review focuses on the pathogenic molecular mechanisms associated with renal lipotoxicity, and presents new insights about potential new therapeutic targets and biomarkers such as microRNAs and long non-coding RNAs, of relevance for the early detection of lipid-associated kidney disease.

In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity. Recently, the evidence suggests that renal lipid accumulation leads to glomerular damage and, more specifically, produces dysfunction in podocytes, key cells that compose and maintain the glomerular filtration barrier. Our aim was to analyze the early mechanisms underlying the development of renal disease associated with the process of lipotoxicity in podocytes. Our results show that treatment of podocytes with palmitic acid produced intracellular accumulation of lipid droplets and abnormal glucose and lipid metabolism. This was accompanied by the development of inflammation, oxidative stress and endoplasmic reticulum stress and insulin resistance. We found specific rearrangements of the actin cytoskeleton and slit diaphragm proteins (Nephrin, P-Cadherin, Vimentin) associated with this insulin resistance in palmitic-treated podocytes. We conclude that lipotoxicity accelerates glomerular disease through lipid accumulation and inflammation. Moreover, saturated fatty acids specifically promote insulin resistance by disturbing the cytoarchitecture of podocytes. These data suggest that renal lipid metabolism and cytoskeleton rearrangements may serve as a target for specific therapies aimed at slowing the progression of podocyte failure during metabolic syndrome.

No abstract

No abstract

Spelling and handwriting are different processes; however, they are learned simultaneously, and numerous studies have shown that they interact. Besides the commonly reported presence of a spelling deficit, previous studies have indicated that handwriting difficulties can also be detected in children with dyslexia. Despite this, this issue has not been sufficiently explored. The goal of the study was to investigate the potential handwriting difficulties met by children with dyslexia and how they might relate to spelling difficulties and to basic graphic skills. Twenty children with dyslexia were compared with a chronological age-matched group and reading level-matched group. Participants completed a spelling-to-dictation task of words and pseudowords, an alphabet writing task, and two graphic tasks. Results showed that children with dyslexia were less accurate and slower in preparing and executing the written response than typically developing peers, but they showed the spelling level expected given their reading ability. Children with dyslexia also performed similarly to children with the same reading level in the alphabet and graphic tasks, with both groups being slower and less fluent than the control age group. Altogether, the results suggest the existence of a delay in the development of handwriting and graphic fluency related to the level of reading and spelling skills rather than the presence of a core deficit affecting fine motor skills in dyslexia. In this sense, it seems that reduced literacy skills can affect the development of other skills that are usually enhanced with handwriting practice, such as fine motor skills.