High-glucose diets induce mitochondrial dysfunction in Caenorhabditis elegans.

Glucose is an important nutrient that dictates the development, fertility and lifespan of all organisms. In humans, a deficit in its homeostatic control might lead to hyperglucemia and the development of obesity and type 2 diabetes, which show a decreased ability to respond to and metabolize glucose. Previously, we have reported that high-glucose diets (HGD) induce alterations in triglyceride content, body size, progeny, and the mRNA accumulation of key regulators of carbohydrate and lipid metabolism, and longevity in Caenorhabditis elegans (PLoS ONE 13(7): e0199888). Herein, we show that increasing amounts of glucose in the diet induce the swelling of both mitochondria in germ and muscle cells. Additionally, HGD alter the enzymatic activities of the different respiratory complexes in an intricate pattern. Finally, we observed a downregulation of ceramide synthases (hyl-1 and hyl-2) and antioxidant genes (gcs-1 and gst-4), while mitophagy genes (pink-1 and dct-1) were upregulated, probably as part of a mitohormetic mechanism in response to glucose toxicity.

Caenorhabditis elegans respond to high-glucose diets through a network of stress-responsive transcription factors.

High-glycemic-index diets, as well as a sedentary lifestyle are considered as determinant factors for the development of obesity, type 2 diabetes, and cardiovascular diseases in humans. These diets have been shown to shorten the life span of C. elegans in a manner that is dependent on insulin signaling, but the participation of other signaling pathways have not been addressed. In this study, we have determined that worms fed with high-glucose diets show alterations in glucose content and uptake, triglyceride content, body size, number of eggs laid, egg-laying defects, and signs of oxidative stress and accelerated aging. Additionally, we analyzed the participation of different key regulators of carbohydrate and lipid metabolism, oxidative stress and longevity such as SKN-1/NRF2, HIF-1/HIF1α, SBP-1/SREBP, CRH-1/CREB, CEP-1/p53, and DAF-16/FOXO, in the reduction of lifespan in glucose-fed worms.

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs.

MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6-20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans.

[Hyperthyrotropinemia in Mexican newborns]. / Hipertirotropinemia en recién nacidos mexicanos.

OBJECTIVE: To assess the differences in the blood concentration levels of the thyroid stimulating hormone and their possible use as an indicator of iodine sufficiency, in a sample of Mexican newborns. MATERIAL AND METHODS: A cross-sectional study was conducted from September 1999 to August 2000, among 25,427 Mexican newborns in the Ministry of Health clinics from 5 states. A total of 8,095 heel-prick and 17,332 umbilical cord blood samples were analyzed. Blood samples were collected in filter paper and processed by enzyme-linked immunosorbent assay. The Mann-Whitney U test and the Kruskal-Wallis test were used for statistical analyses. RESULTS: Hyperthyrotropinemia was found in 9.95% of heel samples and in 24.27% of umbilical cord samples (TSH > 5 microUl/ml). CONCLUSIONS: The percentage of hyperthyrotropinemia observed in this study was higher than that expected in a population with sufficient iodine intake; these findings could be due to poor maternal iodine intake.

Hipertirotropinemia en recién nacidos mexicanos / Hyperthyrotropinemia in Mexican newborns

OBJETIVO: Comunicar las diferencias encontradas en los niveles de concentración sanguínea de la hormona estimulante de la tiroides y su posible uso como indicador del estado de suficiencia de yodo en una muestra de recién nacidos mexicanos. MATERIAL Y MÉTODOS: De septiembre de 1999 a agosto de 2000 se estudiaron 25 427 recién nacidos en unidades asistenciales de la Secretaría de Salud de cinco estados de la República Mexicana. Se analizaron 8 095 muestras de sangre de talón y 17 332 de cordón umbilical. La sangre fue recolectada en papel filtro y procesada mediante ensayo inmunoenzimático. Para el análisis estadístico se emplearon las pruebas U de Mann-Wittney, y de Kruskal-Wallis. RESULTADOS: Se observó que 9.95 por ciento de las muestras de talón y 24.27 por ciento de las de cordón presentaron hipertirotropinemia (TSH>5 æUI/ml). CONCLUSIONES: El porcentaje de muestras de hipertirotropinemia observado es mayor del esperado para una población con aporte suficiente de yodo. Este hallazgo pudiera deberse a una deficiencia en la ingesta materna de yodo