Thurl E. Harris

Increased kidney lipid content during obesity contributes to obesity-related kidney injury but mechanisms of renal lipid accumulation during obesity are incompletely understood. Lean mice also accumulate renal lipid during fasting but how kidney lipid metabolism responds to fasting during obesity is not clear. Mice fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks underwent either ad libitum feeding (NDfd and HFDfd) or an overnight 16 h fast (NDfa and HFDfa) before measurement of renal lipid and kidney transcriptomics by RNA-seq. Renal triglyceride was increased in NDfa mice compared to NDfd mice and also increased in HFDfd mice compared to NDfd. However HFDfa mice did not have greater renal triglyceride than HFDfd mice. RNA-seq demonstrated increased fatty acid metabolism gene expression in NDfa and HFDfa mice compared to the fed controls, but was significantly greater in NDfa than HFDfa mice. Peroxisomal gene expression was also enriched in NDfa compared to HFDfa mice. Expression of peroxisomal fatty acid oxidation genes Acox1 and Ehhadh, increased in NDfa compared to NDfd, while expression of these genes was not changed in HFDfa compared to HFDfd. These results indicate that obesity blunts fasting-induced peroxisomal fatty acid oxidation gene expression.

Metabolic profiling of mammary gland and fecal mircobiome in mice with and without dysbiosis.

Baseline characteristics of bile acid sequestrant (BAS) user and non-user groups.

Characterization of bile acid receptor and invasion, migration, and ECM remodeling-associated protein profiles of breast tumor cells.

Myeloid cell infiltration of lungs in early tumor-bearing mice with or without dysbiosis and treated or untreated with colesevelam.

Reagents and resources information.

Metastatic dissemination of breast tumor cells to multiple sites of metastasis at early and late tumor endpoints following bile acid supplementation.

Metabolic characterization of fecal microbiota transfer (FMT) model.

Patient selection for Epic Cosmos survival analysis, supporting Tables 1 and 2.

Characterization of body composition and microbiome in mice with or without dysbiosis following treatment with colesevelam HCl.