Activation of the LH receptor up regulates the type 2 adiponectin receptor in human granulosa cells

PURPOSE: Adiponectin is a predominantly adipocyte-derived hormone which influences insulin sensitivity and energy homeostasis through at least two receptors, AdipoR1 and AdipoR2. In animal models, adiponectin may regulate ovarian steroidogenesis, folliculogenesis, and ovulation. The receptors AdipoR1 and AdipoR2 are present in the human ovary, but their regulation is unknown. In these studies, we determined the effects of LH receptor activation on the expression and function of the two adiponectin receptors in human granulosa cells. METHODS: Granulosa cells were obtained at the time of oocyte retrieval in women undergoing in vitro fertilization (IVF). Cells were isolated and cultured for 48 h in DMEM/F12 medium with 5 % FBS and 50 ug/ml gentamicin. Medium was changed to low serum for 12 h and cells were treated with hCG (100 ng/ml), forskolin (30 μMol/L), or FSH (1 IU/ml) for 24 h for mRNA experiments. mRNA was isolated and RT PCR was performed using Taqman assays and quantification with the delta delta CT method. For immunocytochemistry, cells were grown on chamber slides and treated with hCG for 1 to 24 h and fixed with acetone. ICC was performed with polyclonal rabbit primary antibodies followed by alexa fluor goat anti-rabbit antibody and imaging with a fluorescence microscope and Zeiss software analysis. 3β-hydroxysteroid dehydrogenase (3βHSD) enzyme activity was determined by measuring the progesterone produced when cells were provided with an excess of 22-hydroxy-cholesterol as substrate following an incubation with hCG (1 IU/ml) and/or adiponectin (10 ng/ml). Progesterone content in the media was determined by ELISA. RESULTS: Messenger RNA for the two Adiponectin receptors is differentially regulated by activation of LHR with hCG treatment. AdipoR2 was increased nearly 4-fold (p < 0.05), whereas AdipoR1 expression was not changed by hCG treatment. Treatment with either FSH or forskolin (an activator of cAMP) had similar effects. Basal AdipoR2 protein was fairly low in granulosa cells in culture however treatment of cells with hCG resulted in a discernible increase in immunodetectable cytoplasmic protein as early as 6 h after treatment and was maintained for at least 24 h. The number of cells positive for AdipoR2 at 6 h increased from a basal of 20 % to almost 60 % (p < 0.05). Adiponectin treatment of hCG-primed cells resulted in increased 3βHSD activity by approximately 60 % over hCG alone and more than 3-fold over basal levels. CONCLUSIONS: AdipoR2 is regulated by the LH receptor function via a cAMP dependant mechanism. Increased expression of adipoR2 prior to and following ovulation may contribute to enhanced 3βHSD activity and increased progesterone secretion by the corpus luteum of the ovary. Dysregulation of adiponectin that may occur with PCOS may impair normal progesterone production

Modeling Pediatric Body Mass Index and Neighborhood Environment at Different Spatial Scales

In public health research, it has been well established that geographic location plays an important role in influencing health outcomes. In recent years, there has been an increased emphasis on the impact of neighborhood or contextual factors as potential risk factors for childhood obesity. Some neighborhood factors relevant to childhood obesity include access to food sources, access to recreational facilities, neighborhood safety, and socioeconomic status (SES) variables. It is common for neighborhood or area-level variables to be available at multiple spatial scales (SS) or geographic units, such as the census block group and census tract, and selection of the spatial scale for area-level variables can be considered as a model selection problem. In this paper, we model the variation in body mass index (BMI) in a study of pediatric patients of the Virginia Commonwealth University (VCU) Medical Center, while considering the selection of spatial scale for a set of neighborhood-level variables available at multiple spatial scales using four recently proposed spatial scale selection algorithms: SS forward stepwise regression, SS incremental forward stagewise regression, SS least angle regression (LARS), and SS lasso. For pediatric BMI, we found evidence of significant positive associations with visit age and black race at the individual level, percent Hispanic white at the census block group level, percent Hispanic black at the census tract level, and percent vacant housing at the census tract level. We also found significant negative associations with population density at the census tract level, median household income at the census tract level, percent renter at the census tract level, and exercise equipment expenditures at the census block group level. The SS algorithms selected covariates at different spatial scales, producing better goodness-of-fit in comparison to traditional models, where all area-level covariates were modeled at the same scale. These findings underscore the importance of considering spatial scale when performing model selection

POSITION STATEMENT: Glucose Intolerance in Polycystic Ovary Syndrome-A Position Statement of the Androgen Excess Society

Objectives: Women with polycystic ovarian syndrome (PCOS) are at increased risk for developing glucose intolerance and type 2 diabetes mellitus (DM). Recommendations for the timing and method of screening have varied. The purpose of this statement is to determine the optimal screening method, timing of screening, and treatment modalities for impaired glucose tolerance (IGT) among women with PCOS. Participants: The expert panel was appointed by the Androgen Excess Society (AES) to review the literature and make recommendations based on the available evidence. Meetings were open, and there was no funding for the panel. Evidence: A systematic review was conducted of the published, peerreviewed medical literature using MEDLINE to identify studies that addressed the prevalence, risk factors, testing, and treatment for IGT in both adults and adolescents with PCOS. Unpublished data were not considered. Consensus Process: The panel held meetings to review the literature and draft the statement as a committee. The AES board members reviewed and critiqued the manuscript, and changes were made based on their comments. Conclusions: The panel recommends that all patients with PCOS be screened for IGT with a 2-h oral glucose tolerance test. A few members of the AES board recommend alternatively screening women with PCOS for IGT and type 2 DM using an oral glucose tolerance test only in patients with a body mass index of 30 kg/m 2 or greater or in lean patients with additional risk factors. Patients with normal glucose tolerance should be rescreened at least once every 2 yr, or more frequently if additional risk factors are identified. Those with IGT should be screened annually for development of type 2 DM. PCOS patients with IGT should be treated with intensive lifestyle modification and weight loss and considered for treatment with insulinsensitizing agents. T HE POLYCYSTIC ovarian syndrome (PCOS) is a common endocrinopathy, affecting approximately 5-10% of women of reproductive age (1-4). In its classical form, the syndrome is characterized by oligo-or anovulation, biochemical or clinical hyperandrogenism, and polycystic ovarian morphology on ultrasonography (5). Although much remains unknown regarding the underlying pathophysiology of PCOS, a form of insulin resistance intrinsic to the syndrome appears to play a central role in its development. Among many women with PCOS, the observed insulin resistance is partially explained by excess adiposity; however, it is increasingly recognized that even lean women with PCOS have increased insulin resistance compared with normal controls (6). Given the significant metabolic burden of insulin resistance seen in women with PCOS, affected women may have an increased risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). IGT is a known risk factor for type 2 DM and the development of cardiovascular disease (7). Because IGT is often asymptomatic, the screening of women with PCOS for IGT has been recommended; however, recommendations have varied regarding the timing and method of screening for IGT (8, Process A systematic review was conducted of the published, peerreviewed medical literature to identify studies assessing the prevalence and risk factors for IGT in patients with PCOS, as well as the testing and treatment of IGT in both adults and adolescents using MEDLINE databases. To review the natural history of PCOS and IGT, MEDLINE was searched from 1966 through 2007. Medical Subject Headings (MeSH) used included polycystic ovary syndrom

The role of parents in behavioral treatment for adolescent obesity: design and rationale for the TEENS+ randomized clinical trial

Abstract Background There is an urgent need for innovative approaches to adolescent obesity treatment, particularly among individuals from racially and ethnically marginalized backgrounds, who face increased risk of obesity and its associated morbidity and mortality. There is a particular dearth of research on the long-term efficacy of adolescent obesity treatments. Further, research and clinical practice guidelines consistently recommend parents’ inclusion in their adolescents’ obesity treatment, yet the most effective strategy to engage parents in adolescent obesity treatment remains unclear. Towards that end, this investigation will conduct a fully-powered, randomized clinical trial to examine the efficacy of two distinct approaches to involving parents in their adolescents’ obesity treatment. Methods Participants will be 210 12-16 year old adolescents (body mass index [BMI]≥85th percentile) and parents (BMI≥25 kg/m2) with overweight or obesity. Dyads will be randomized to one of two 4-month treatments: 1) TEENS+Parents as Coaches (PAC), engaging parents as helpers in their child’s weight management via parent skills training based on authoritative parenting, or 2) TEENS+Parent Weight Loss (PWL), engaging parents in their own behavioral weight management. All adolescents will participate in the TEENS+ protocol, which includes nutrition education with dietary goals, supervised physical activity, and behavioral support, and integrates motivational interviewing to enhance treatment engagement. Assessments of anthropometrics, dietary intake, physical activity, parenting and home environment variables will be completed at 0, 2, 4, 8, and 12 months with the primary endpoint at 12-month follow-up. Discussion Results of this investigation have the potential to significantly advance science in this area and ultimately inform clinical practice guidelines related to the role of parents in adolescent obesity treatment. Trial registration Clinicaltrials.gov NCT03851796. Registered: February 22, 2019

A scalable, virtual weight management program tailored for adults with type 2 diabetes: effects on glycemic control

Abstract Background The objective was to test the efficacy of a scalable, virtually delivered, diabetes-tailored weight management program on glycemic control in adults with type 2 diabetes (T2D). Methods This was a single arm, three-site clinical trial. Participants had baseline HbA1c between 7–11% and BMI between 27–50 kg/m2. Primary outcome was change in HbA1c at 24 weeks. Secondary outcomes were changes in body weight, waist circumference, the Diabetes Distress Scale (DDS), quality of life (IWQOL-L), and hunger (VAS). Generalized linear effects models were used for statistical analysis. Results Participants (n = 136) were 56.8 ± 0.8 y (Mean ± SEM), 36.9 ± 0.5 kg/m2, 80.2% female, 62.2% non-Hispanic white. Baseline HbA1c, weight, and total DDS score were 8.0 ± 0.09%, 101.10 ± 1.47 kg, and 2.35 ± 0.08, respectively. At week 24, HbA1c, body weight, and total DDS decreased by 0.75 ± 0.11%, 5.74 ± 0.50%, 0.33 ± 0.10 units, respectively (all p < 0.001). Also, at week 24, quality of life increased by 9.0 ± 1.2 units and hunger decreased by 14.3 ± 2.4 units, (both p < 0.0001). Conclusions The scalable, virtually delivered T2D-tailored weight management program had favorable and clinically meaningful effects on glycemic control, body weight, and psychosocial outcomes