Bioelectrical impedance analysis and anthropometry for the determination of body composition in rats: effects of high-fat and high-sucrose diets

OBJECTIVE: The aim of the present study was to determine the impedance of Wistar rats treated with high-fat and high-sucrose diets and correlate their biochemical and anthropometric parameters with chemical analysis of the carcass. METHODS: Twenty-four male Wistar rats were fed a standard (AIN-93), high-fat (50% fat) or high-sucrose (59% of sucrose) diet for 4 weeks. Abdominal and thoracic circumference and body length were measured. Bioelectrical impedance analysis was used to determine resistance and reactance. Final body composition was determined by chemical analysis. RESULTS: Higher fat intake led to a high percentage of liver fat and cholesterol and low total body water in the High-Fat group, but these changes in the biochemical profile were not reflected by the anthropometric measurements or bioelectrical impedance analysis variables. Anthropometric and bioelectrical impedance analysis changes were not observed in the High-Sucrose group. However, a positive association was found between body fat and three anthropometric variables: body mass index, Lee index and abdominal circumference. CONCLUSION: Bioelectrical impedance analysis did not prove to be sensitive for detecting changes in body composition, but body mass index, Lee index and abdominal circumference can be used for estimating the body composition of rats

CRISPR editing of sftb-1/SF3B1 in Caenorhabditis elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing

SF3B1 is the most frequently mutated splicing factor in cancer. Mutations in SF3B1 likely confer clonal advantages to cancer cells but they may also confer vulnerabilities that can be therapeutically targeted. SF3B1 cancer mutations can be maintained in homozygosis in C. elegans, allowing synthetic lethal screens with a homogeneous population of animals. These mutations cause alternative splicing (AS) defects in C. elegans, as it occurs in SF3B1-mutated human cells. In a screen, we identified RNAi of U2 snRNP components that cause synthetic lethality with sftb-1/SF3B1 mutations. We also detected synthetic interactions between sftb-1 mutants and cancer-related mutations in uaf-2/U2AF1 or rsp-4/SRSF2, demonstrating that this model can identify interactions between mutations that are mutually exclusive in human tumors. Finally, we have edited an SFTB-1 domain to sensitize C. elegans to the splicing modulators pladienolide B and herboxidiene. Thus, we have established a multicellular model for SF3B1 mutations amenable for high-throughput genetic and chemical screens