Biology subjects

Raho, I.

Publications and source records attributed to Raho, I..

2 recordsLinked to original sources

bioRxiv2024

Long-term disruption of glucose homeostasis in a rodent model of preterm birth.

Around 1 of every 10 babies is born preterm, and the incidence of preterm birth has been rising. The long-term consequences of preterm survivors are not fully understood. Preterm birth is proven to be associated with metabolic diseases and related disorders later in life. Preterm newborns are susceptible to perinatal inflammatory events such as chorioamnionitis, hypoxia-ischemia, and sepsis. We hypothesized that perinatal inflammation has a role in the developmental programming of metabolic diseases and related disorders. In the present study, perinatal inflammation was modeled by systemic administration of IL-1{beta} in mice. We observed a pronounced sexual dimorphism where only the males presented significant insulin resistance and glucose intolerance accompanied by leptin resistance in the long term following perinatal inflammation exposure. Adiposity and energy homeostasis were intact. It showed that perinatal inflammation selectively contributes to the long-term dysregulation of glucose metabolism in a sex-dependent manner. The underlying mechanism might be linked with hypothalamic inflammation and upregulated circulating CCL5. Metformin treatment might be optional to treat insulin resistance resulting from perinatal inflammation. HighlightsO_LIPerinatal inflammation is common in preterm infants, often leading to perinatal brain injuries. However, the long-term metabolic outcomes of these infants are not fully revealed. C_LIO_LIWe explored the long-term metabolic outcomes in mice with perinatal IL-1{beta} exposure and sought its association with inflammation. C_LIO_LIPerinatal inflammation has a profound and deleterious role in glucose metabolism in a sex-dependent and time-dependent manner. C_LIO_LIPerinatal inflammation might be a risk factor for metabolic disorders in preterm survivors. C_LI

physiology↗

bioRxiv2021

Hepatocyte serine palmitoyl transferase 2 deficiency promotes liver C16:0-ceramide accumulation through sphingomyelin hydrolysis and leads to liver damage and dysfunction in mice

Ceramides (Cer) have been shown as lipotoxic inducers, which disturb numerous cell signalling pathways especially insulin signalling pathway leading to metabolic disorders such as type 2 diabetes. In this study, we aimed to determine the role of de novo hepatic Cer synthesis on energy and liver homeostasis in mice. We generated mice lacking serine palmitoyltransferase 2 (Sptlc2), the rate limiting enzyme of Cer de novo synthesis, in hepatocytes. Despite lower expression of hepatic Sptlc2, we observed an increased concentration of hepatic Cer, especially C16:0-Cer and C18:0-Cer associated with an increased neutral sphingomyelinase 2 expression, and a decreased sphingomyelin content in the liver. Sptlc2{Delta}Hep mice were protected against obesity induced by high fat diet. Bile acid (BA) hydrophobicity was drastically decreased in KO mice, and was associated with a defect in lipid absorption. In addition, an important increase of tauro-muricholic acid in BA pool composition was associated with a downregulation of the nuclear BA receptor FXR target genes. Sptlc2 deficiency also enhanced glucose tolerance and attenuated hepatic glucose production. Finally, Sptlc2 disruption promoted apoptosis, inflammation and progressive development of hepatic fibrosis worsening with age. Our data suggest a compensatory mechanism to regulate hepatic Cer content from sphingomyelin hydrolysis, with deleterious impact on liver homeostasis. In addition, our results show the implication of hepatic sphingolipid modulation on BA metabolism and hepatic glucose production in an insulinin-dependent manner, which demonstrates the role of Cer in many metabolic functions still under-researched.

physiology↗