Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria

Epigenetic modifications (e.g. DNA methylation) in NAFLD and their contribution to disease progression and extrahepatic complications are poorly explored. Here, we use an integrated epigenome and transcriptome analysis of mouse NAFLD hepatocytes and identify alterations in glyoxylate metabolism, a pathway relevant in kidney damage via oxalate release—a harmful waste product and kidney stone-promoting factor. Downregulation and hypermethylation of alanine-glyoxylate aminotransferase (Agxt), which detoxifies glyoxylate, preventing excessive oxalate accumulation, is accompanied by increased oxalate formation after metabolism of the precursor hydroxyproline. Viral-mediated Agxt transfer or inhibiting hydroxyproline catabolism rescues excessive oxalate release. In human steatotic hepatocytes, AGXT is also downregulated and hypermethylated, and in NAFLD adolescents, steatosis severity correlates with urinary oxalate excretion. Thus, this work identifies a reduced capacity of the steatotic liver to detoxify glyoxylate, triggering elevated oxalate, and provides a mechanistic explanation for the increased risk of kidney stones and chronic kidney disease in NAFLD patients

Avaliação nutricional da silagem de grãos úmidos de milho com diferentes teores de óleo para leitões na fase de creche Nutritional evaluation of high moisture corn silage with different oil contents for piglets in nursery phase

Utilizaram-se 60 leitões mestiços (Large White x Landrace), desmamados com peso inicial médio de 7,9kg, no experimento de desempenho e 20 leitões mestiços, com peso inicial médio de 16,8kg, no experimento de digestibilidade para avaliar a silagem de grãos úmidos de milho com diferentes teores de óleo. O delineamento experimental foi o de blocos ao acaso em ambos os experimentos avaliou-se o valor nutricional das silagens e dos milhos secos com teor normal (4,3%EE na MS) ou elevado de óleo (5,66%EE na MS). Não houve efeito dos tratamentos sobre o consumo diário de ração e no ganho de peso diário nos períodos de 0 a 9 e 0 a 31 dias. Os leitões apresentaram melhor conversão alimentar em ambos os períodos estudados, quando receberam silagem e no período de 0 a 9 dias, quando foram alimentados com milho com teor mais alto de óleo. As frações digestível e metabolizável da energia foram influenciadas pelo processamento, sendo que a ensilagem proporcionou melhor aproveitamento da energia, independentemente do teor de óleo presente nos grãos.<br>Sixty crossbred weaned pigs (Large White x Landrace) average initial body weight of 7.9kg and 20 crossbred pigs average initial body weight of 16.8kg were used in the performance and digestibility experiments, respectively, to evaluate high-moisture corn silage with different oil contents. The nutritional value of high-moisture corn silage and dry corn with normal (4.3% EE in DM) or higher (5.66% EE in DM) oil contents were analyzed. The treatments had no effect on either average daily feed intake (ADFI) or average daily gain (ADG) from 0 to 9 and 0 to 31 days. The piglets had higher feed/weight gain in both periods when fed silage and in the period from 0 to 9 days when fed higher oil content corn. In the digestibility experiment only the digestible and metabolizable fractions of energy were affected by the processing method and the silage provided higher energy utilization regardless of the oil content in the grains