Author Interviews, Endocrinology, Weight Research / 27.03.2019

MedicalResearch.com Interview with: Liya Kerem, MD Fellow, Pediatric Endocrine Unit Massachusetts General Hospital for Children Harvard Medical School MedicalResearch.com: What is the background for this study?   Response: The hypothalamic neurohormone Oxytocin (OXT), shown to decrease food intake in animals and humans, is a promising novel treatment for obesity. We previously showed that in men with overweight/obesity, intranasal (IN)OXT reduced the fMRI activation in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system, in response to high-calorie food vs non-food visual stimuli. Here, we employed fMRI functional connectivity analysis, which better characterizes the exchange in information between neural systems in a context-dependent manner. We hypothesized that Oxytocin would reduce the functional connectivity of the VTA with food motivation brain areas in response to high-calorie foods.  (more…)
Author Interviews, Duke, Endocrinology, Environmental Risks, Thyroid Disease, Weight Research / 27.03.2019

MedicalResearch.com Interview with: Christopher D. Kassotis, Ph.D. NRSA Postdoctoral Research Scholar Stapleton Lab Duke University Nicholas School of the Environment Durham, NC 27708  MedicalResearch.com: What is the background for this study? What are the main findings?
  • So this was something that Heather Stapleton had been curious about for years, as she's been one of several researchers characterizing the hundreds of chemicals that have been measured in indoor house dust. Before I came to Duke, one of her PhD students had measured the ability of many common indoor contaminants to activate the peroxisome proliferator activated receptor gamma (PPARg). The majority of these chemicals did, often quite well, which led to them testing indoor house dust extracts, also finding that the majority of dust extracts were also able to do so at very low levels. As PPARg is often considered the master regulator of fat cell development, the next obvious question was whether these common contaminants (and house dust) could promote fat cell development in cell models. My first work at Duke evaluated a suite of common indoor contaminants, finding that many of these chemicals could promote fat cell development, and that low levels of house dust extracts did as well.
  • We next explored this more systematically in a group of adults involved in a thyroid cancer cohort (this was just recently published in Science of the Total Environment: https://www.sciencedirect.com/science/article/pii/S0048969719307715?dgcid=author
  • In this study we evaluated the extent to which house dust extracts could promote fat cell development in a common cell model, and associated this with the metabolic health of adults living in these homes. We found that the greater extent of fat cell development was associated with significantly greater thyroid stimulating hormone concentrations (control residents only, with no evidence of thyroid dysfunction) and lower free triiodothyronine (T3) and thyroxine (T4). We further found a significant and positive association between extent of fat cell development and the body mass index (BMI) of all adults in the study. So this suggested that the indoor environment might play a role in the BMI and metabolic health of residents, and we next wondered if this would be more pronounced in children, who may be exposed to these contaminants during a critical window of development.
  • The next step, for our current work, was to substantiate these effects in a larger group of households, each with children.
  • Our major conclusions thus far have been that ~80% of house dust extracts promote significant fat cell development in a cell model - either via development from precursor cells into mature fat cells, measured via accumulation of lipids into the cells, or via the proliferation of those precursor fat cells. We also reported positive correlations of fat cell development with the concentrations of 70 different contaminants in the dust from these homes, suggesting that mixtures of contaminants are likely all acting weakly to produce these effects in combination. We’ve also begun to assess the other chemicals present in dust - chemistry can be either targeted (measuring concentrations of specific known chemicals in a sample), or non-targeted, where you try and determine the identity of the other chemicals in a sample. This has greater utility for identifying many more chemicals, though you will often not get chemical concentrations from this, nor absolute confirmed identification - just varying degrees of certainty based on evidence. Thus far we report approximately 35,000 chemicals in house dust samples across this study, and differential analyses have begun to pick out the few (less than 10 in each case) chemicals most differentially expressed between samples that exhibit high degrees of fat cell development in the lab vs inactive samples, for example, or which are differentially present in the homes of children categorized as obese or overweight. We are now working to confirm identity of these select contaminants that are more likely to be causative factors in the results we have observed.
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Author Interviews, Endocrinology, Gender Differences, Hormone Therapy / 26.03.2019

MedicalResearch.com Interview with: Joshua Safer, MD, Executive Director Center for Transgender Medicine and Surgery Mount Sinai Health System Senior Faculty, Medicine, Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? What are the main findings? Response: The standard trans feminizing hormone regimen includes estrogen both to suppress testosterone and so that the individual has sufficient circulating sex hormone in the body for good bone health. After orchiectomy, there is no need to suppress testosterone because the levels are very low and it is common to cut the estrogen dose in half.  Cis women with premature ovarian failure often take about 2 mg of estradiol daily so that dose has seemed reasonable for trans women without testes.  However, when my co-author Sira Korpaisarn and I checked estradiol levels and gonadotropins (pituitary hormones, LH and FSH) as a guide to dosing, we found that based on that testing, trans women may require higher doses of estrogens than the 2 mg that we expected. (more…)
Author Interviews, Endocrinology, Genetic Research / 24.03.2019

MedicalResearch.com Interview with: Emily J. Gallagher, MD Assistant Professor of Medicine Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai  MedicalResearch.com: What is the background for this study? Response: Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2) is an inherited endocrine disorder characterized by the development of pheochromocytoma, medullary thyroid carcinoma (MTC) and parathyroid tumors. It occurs due to activating missense variants in the RET gene. The estimated prevalence of MEN2 is 1 per 30,000 in the general population. Through a collaboration between The Center for Genomic Health, the Charles Bronfman Institute for Personalized Medicine, and the Division of Endocrinology at Mount Sinai, our aim was to investigate the prevalence and clinical manifestations of pathogenic RET variants in the multi-ethnic BioMe Biobank. The BioMe Biobank is an electronic health record-linked biobank with exome sequencing data available for more than 30,000 patients recruited across The Mount Sinai Health System. (more…)