Project description:Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays. Human liver samples were obtained from 5 lean control subjects undergoing elective cholecystectomy and 13 obese subjects (with or without Type 2 diabetes) undergoing gastric bypass surgery. Subjects with diabetes were classified as either well-controlled or poorly-controlled.
Project description:Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. In this study liver metabolic activity and functionality in NAFLD was charted by integrating global transcriptomic data within a genome-scale model of human metabolism. Gene expression was measured in the human liver of eight subjects with extreme steatosis diagnosed with NAFLD (liver fat % range 20-80%), and eight healthy, but obese subjects with low liver fat content (liver fat % range 0-10%). This dataset is part of the TransQST collection.
Project description:Affymetrix miRNA 3.0 array profiling of adipocyte-derived exosomes from obese and lean human subjects. We used miRNA arrays to profile exosomes shed from obese and lean human visceral fat that was cultured for 60 minutes.
Project description:Affymetrix miRNA 3.0 array profiling of adipocyte-derived exosomes from obese and lean human subjects. We used miRNA arrays to profile exosomes shed from obese and lean human subcutaneous fat that was cultured for 60 minutes.
Project description:Patients with long-duration diabetes develop cardiovascular complications resulting in highly increased mortality and complications which affect the kidneys, eyes and peripheral nerves associated with high morbidity. Among the diabetic complications, damage in the eye, diabetic retinopathy, is the most common microvascular complication of diabetes. Diabetic retinopathy is a leading cause of vision-loss globally. It is characterized by a number of different patho-mechanisms including changes in vascular permeability, capillary degeneration, and finally at a late stage overshooting formation of new blood vessels. This expression analysis focused on the use of different experimental models for Diabetes Mellitus and its complications (for a review see 1: Al-Awar et al: Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; doi: 10.1155/2016/9051426). By that, we wanted to uncover the relative contributions of systemic hyperinsulinaemia and/or hyperglycemia to molecular regulations. The following models have been used: As insulinopenic, hyperglycemic model reflecting Type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p.) were used. Wistar rats without STZ injection served as non-diabetic controls. Male obese ZDF rats (Fa/Fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male lean ZDF rats (Fa/-) served as non-diabetic controls. Male obese ZF rats (Fa/Fa) hyperglycemia were used reflecting euglycemia and severe insulin resistance. Male lean ZF rats (Fa/-) served as controls. ZDF and ZF rats were obtained in two genotypes, obese (genotype fa/fa) and lean littermates (genotype Fa/?). All rats were housed in standard cages under a normal light-dark cycle for 16 weeks. All animals had free access to food and water. ZF and Wistar rats received a standard chow (Ssniff R/M) and ZDF rats received Purina 5008 chow. A group size of n=8 were used for all study groups. Wistar rats were rendered type-1 like hyperglycemic and hypoinsulinemic via a single injection of streptocotocin (STZ, 60mg/kg; i.p.) at 7 weeks of age. Obese ZDF rats (fa/fa) develop spontaneously a type-2 diabetes phenotype with persisting hyperglycemia and transient hyperinsulinemia (hyperglycemic, hypoinsulinemic). Obese ZF rats (fa/fa) develop insulin resistance with permanent hyperinsulinemia without concomitant hyperglycemia and no overt diabetes phenotype. Non STZ treated Wistar rats, lean ZDF littermates (Fa/?), and lean ZF littermates (Fa/?) served as controls. All groups were kept for 12 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays.
Project description:Affymetrix miRNA 3.0 array profiling of adipocyte-derived exosomes from obese and lean human subjects. We used miRNA arrays to profile exosomes shed from obese and lean human subcutaneous fat that was cultured for 60 minutes. Human obese and lean subcutaneous fat were surgically acquired, dissected, and promptly cultured for 60 minutes. We used the culture supernatants for exosome purification and isolation using ExoQuick-TC Precipitation Solution.
Project description:Animal studies have linked disturbed adipose tissue clock gene rhythms to the pathophysiology of the metabolic syndrome. However, data on molecular clock rhythms in human patients are limited. Therefore, in a standardized real life setting, we compared diurnal gene expression profiles in subcutaneous adipose tissue between obese patients with type 2 diabetes and age-matched healthy lean control subjects, using RNA sequencing. In patients, 1.8% (303 genes) of expressed genes showed significant diurnal rhythms, compared to 8.4% (1421 genes) in healthy controls. In patients, the core clock genes showed reduced amplitude oscillations. Enrichment analysis revealed a loss of rhythm in canonical metabolic pathways including AMPK signaling and cAMP mediated signaling in patients. In conclusion, we provide the first transcriptomics atlas of human adipose tissue diurnal rhythms, and show evidence of decreased diurnal clock and metabolic gene expression rhythms in subcutaneous adipose tissue of obese patients with type 2 diabetes.
Project description:Affymetrix miRNA 3.0 array profiling of adipocyte-derived exosomes from obese and lean human subjects We used miRNA arrays to profile exosomes shed from obese and lean human visceral and subcutaneous fat that was cultured for 60 minutes. Human obese and lean visceral and subcutaneous fat were surgically acquired, dissected, and promptly cultured for 60 minutes. We used the culture supernatants for exosome purification and isolation using ExoQuick-TC Precipitation Solution