This study evaluated the modulatory effect of African star apple fruit (ASAF) pulp inclusive diet on biomolecules associated with reproductive function in the testis and epididymis of high‐fat diet/streptozotocin‐induced diabetic male rats. The rats were divided into seven groups: control, diabetic control, diabetic rats treated with metformin, diabetic rats served with diet having 5 and 10% ASAF, respectively, and control rats served with diet containing 5%, and 10% ASAF respectively for 14 days. There were noticeable decrease in sperm parameters, reproductive hormone, glycogen, nitric oxide, total thiol, nonprotein thiol levels, and testicular 3β‐ and 17β‐hydroxysteroid dehydrogenase activities and concomitant increase in cholesterol, reactive oxygen species, malondialdehyde levels, and arginase activity compared to the control. Nevertheless, ASAFs reversed all these parameters toward the control levels. Therefore, these findings suggest that ASAF pulp‐supplemented diet might be an active approach in controlling male reproductive dysfunction induced by diabetes. Practical applications The results suggest that ASAF pulp‐supplemented diet might be an active approach in controlling male reproductive dysfunction induced by diabetes through alterations in the levels of blood glucose, glycogen, cholesterol, nitric oxide, reproductive hormones, activities of steroidogenic enzymes, arginase, and sperm characteristics as well as the antioxidant status in the testes and epididymis.

Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity—a worldwide public health concern—is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas–Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner.

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Background Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity, a worldwide public health concern, is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. Methods RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; Body mass index (BMI) was calculated and categorized as normal, overweight, and obese. Results We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing effects on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Conclusions Thus, we conclude that obesity has CMS-specific effects on the CRC tumor transcriptome.

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