Acute Modulation of Adipose Tissue Lipolysis by Intravenous Estrogens

Objective: The aim of this study was to determine whether intravenous (IV) conjugated estrogens (EST) acutely enhance the suppression of whole-body or regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal women. Research Methods and Procedures: We assessed whole-body lipolysis by [2H5]glycerol rate of appearance (GlycRA) and abdominal and femoral SAT lipolysis (interstitial glycerol; GlycIS) by subcutaneous microdialysis. Postmenopausal women (n = 12) were studied on two occasions, with IV EST or saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40 mU/m2/ min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and recovery of [13C] glycerol during microdialysis were used to assess blood flow changes and interstitial glycerol concentrations, respectively. Results: Compared with CON, EST did not affect systemic basal or insulin-mediated suppression of lipolysis (GlycRA) or SAT nutritive blood flow. Basal GlycIS in SAT was reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT was not significantly influenced by EST. Discussion: These findings suggest that estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but do not alter whole-body or SAT suppression of lipolysis by insulin. Originally published Obesity (Silver Spring), Vol. 14, No. 12, Dec 200

Morbidly Obese Patients—Who Undergoes Bariatric Surgery?

Treatment seeking patients with severe obesity might choose between specialized medical treatment and surgical treatment. Knowledge of what distinguishes patients that choose either treatment is sparse, with greater understanding also needed on what consequences this choice has for the prevalence, remission and new onset of comorbidities, as well as for the bioavailability of drugs. This has prompted the studies in Gunn Signe Jakobsen and her coauthors work on treatment seeking patients with severe obesity focusing on the prevalence of comorbidities, changes in the use of drugs for hypertension, diabetes and dyslipidaemia, as well as changes in bioavailability of atorvastatin. The methods used in the studies in the thesis; "Bariatric surgery and specialized medical treatment for severe obesity Impact on cardiovascular risk factors and postsurgical pharmacokinetics of atorvastatin "; are a cross-sectional study, a registry based cohort study and a prospective pharmacokinetic study. The results of the studies presented were: - The type and number of comorbidities associated with morbid obesity did not necessarily impact upon choice of treatment, but there was an increased odds for choosing surgery for patients with higher BMI, younger age and earlier onset of obesity. - Patients opting for bariatric surgery as opposed to specialized medical treatment had higher odds of experiencing remission, and significantly lower odds for new-onset of drug treated hypertension, diabetes and dyslipidaemia. Bariatric surgery seemed to not only induce remission but was also effective in preventing disease. - The bioavailability of atorvastatin was increased after bariatric surgery, with a normalization in the long term. This knowledge can give a better understanding of the population of patients seeking treatment for severe obesity and should be included in the shared decision process when helping the patient identify their preferences for treatment of severe obesity in the context of their values

Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signaling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no growth hormone-dependent STATS signaling respectively. These mutants result in altered liver metabolism, obesity and insulin resistance

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD