Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E2), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX). We used an alternate approach to isolate the individual and combined contributions of FSH and E2 in mediating energy imbalance and changes in tissue-level metabolic health. Female Wistar rats were ovariectomized and given the gonadotropin releasing hormone (GnRH) antagonist degarelix to suppress FSH production. E2 and FSH were then added back individually and in combination for a period of 3 wk. Energy balance, body mass composition, and transcriptomic profiles of individual tissues were obtained. In contrast to previous studies, suppression and replacement of FSH in our paradigm had no effect on body weight, body composition, food intake, or energy expenditure. We did, however, observe organ-specific effects of FSH that produced unique transcriptomic signatures of FSH in retroperitoneal white adipose tissue. These included reductions in biological processes related to lipogenesis and carbohydrate transport. In addition, rats administered FSH had reduced liver triglyceride concentration (P < 0.001), which correlated with FSH-induced changes at the transcriptomic level. Although not appearing to modulate energy balance after loss of ovarian function in rats, FSH may still impart tissue-specific effects in the liver and white adipose tissue that might affect the metabolic health of those organs.NEW & NOTEWORTHY We find no effect of follicle-stimulating hormone (FSH) on energy balance using a novel model in which rats are ovariectomized, subjected to gonadotropin-releasing hormone antagonism, and systematically given back FSH by osmotic pump. However, tissue-specific effects of FSH on adipose tissue and liver were observed in this study. These include unique transcriptomic signatures induced by the hormone and a stark reduction in hepatic triglyceride accumulation.

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer.

BACKGROUND: Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion. METHODS: We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. We tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors. RESULTS: In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (i.e., BDNF, TNFα, FGF-2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1 in mammary adipose, and reduced phosphorylated FGFR indicating reduced FGF signaling in tumors. CONCLUSIONS: Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multi-factorial, and that weight maintenance during the peri-/postmenopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease.

Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to ad libitum, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.

UK Healthcare Workers' Experiences of Major System Change in Elective Surgery During the COVID-19 Pandemic: Reflections on Rapid Service Adaptation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted the delivery of elective surgery in the United Kingdom. The majority of planned surgery was cancelled or postponed in March 2020 for the duration of the first wave of the pandemic. We investigated the experiences of staff responsible for delivering rapid changes to surgical services during the first wave of the pandemic in the United Kingdom, with the aim of developing lessons for future major systems change (MSC). METHODS: Using a rapid qualitative study design, we conducted 25 interviews with frontline surgical staff during the first wave of the pandemic. Framework analysis was used to organise and interpret findings. RESULTS: Staff discussed positive and negative experiences of rapid service organisation. Clinician-led decision-making, the flexibility of individual staff and teams, and the opportunity to innovate service design were all seen as positive contributors to success in service adaptation. The negative aspects of rapid change were inconsistent guidance from national government and medical bodies, top-down decisions about when to cancel and restart surgery, the challenges of delivering emergency surgical care safely and the complexity of prioritising surgical cases when services re-started. CONCLUSION: Success in the rapid reorganisation of elective surgical services can be attributed to the flexibility and adaptability of staff. However, there was an absence of involvement of staff in wider system-level pandemic decision-making and competing guidance from national bodies. Involving staff in decisions about the organisation and delivery of MSC is essential for the sustainability of change processes.

Breast Cancer Endocrine Therapy Promotes Weight Gain With Distinct Adipose Tissue Effects in Lean and Obese Female Mice.

Breast cancer survivors treated with tamoxifen and aromatase inhibitors report weight gain and have an elevated risk of type 2 diabetes, especially if they have obesity. These patient experiences are inconsistent with, preclinical studies using high doses of tamoxifen which reported acute weight loss. We investigated the impact of breast cancer endocrine therapies in a preclinical model of obesity and in a small group of breast adipose tissue samples from women taking tamoxifen to understand the clinical findings. Mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in mesenchymal stem cells from adipose tissue, endocrine therapy was associated with adipose accumulation and more preadipocytes compared with estrogen-treated control mice but resulted in fewer adipocyte progenitors only in the context of HFHS. Analysis of subcutaneous adipose stromal cells revealed diet- and treatment-dependent effects of endocrine therapies on various cell types and genes, illustrating the complexity of adipose tissue estrogen receptor signaling. Breast cancer therapies supported adipocyte hypertrophy and associated with hepatic steatosis, hyperinsulinemia, and glucose intolerance, particularly in obese females. Current tamoxifen use associated with larger breast adipocyte diameter only in women with obesity. Our translational studies suggest that endocrine therapies may disrupt adipocyte progenitors and support adipocyte hypertrophy, potentially leading to ectopic lipid deposition that may be linked to a greater type 2 diabetes risk. Monitoring glucose tolerance and potential interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.

Use of Iris Scanning for Biometric Recognition of Healthy Adults Participating in an Ebola Vaccine Trial in the Democratic Republic of the Congo: Mixed Methods Study.

BACKGROUND: A partnership between the University of Antwerp and the University of Kinshasa implemented the EBOVAC3 clinical trial with an Ebola vaccine regimen administered to health care provider participants in Tshuapa Province, Democratic Republic of the Congo. This randomized controlled trial was part of an Ebola outbreak preparedness initiative financed through Innovative Medicines Initiative-European Union. The EBOVAC3 clinical trial used iris scan technology to identify all health care provider participants enrolled in the vaccine trial, to ensure that the right participant received the right vaccine at the right visit. OBJECTIVE: We aimed to assess the acceptability, accuracy, and feasibility of iris scan technology as an identification method within a population of health care provider participants in a vaccine trial in a remote setting. METHODS: We used a mixed methods study. The acceptability was assessed prior to the trial through 12 focus group discussions (FGDs) and was assessed at enrollment. Feasibility and accuracy research was conducted using a longitudinal trial study design, where iris scanning was compared with the unique study ID card to identify health care provider participants at enrollment and at their follow-up visits. RESULTS: During the FGDs, health care provider participants were mainly concerned about the iris scan technology causing physical problems to their eyes or exposing them to spiritual problems through sorcery. However, 99% (85/86; 95% CI 97.1-100.0) of health care provider participants in the FGDs agreed to be identified by the iris scan. Also, at enrollment, 99.0% (692/699; 95% CI 98.2-99.7) of health care provider participants accepted to be identified by iris scan. Iris scan technology correctly identified 93.1% (636/683; 95% CI 91.2-95.0) of the participants returning for scheduled follow-up visits. The iris scanning operation lasted 2 minutes or less for 96.0% (656/683; 95% CI 94.6-97.5), and 1 attempt was enough to identify the majority of study participants (475/683, 69.5%; 95% CI 66.1-73.0). CONCLUSIONS: Iris scans are highly acceptable as an identification tool in a clinical trial for health care provider participants in a remote setting. Its operationalization during the trial demonstrated a high level of accuracy that can reliably identify individuals. Iris scanning is found to be feasible in clinical trials but requires a trained operator to reduce the duration and the number of attempts to identify a participant. TRIAL REGISTRATION: ClinicalTrials.gov NCT04186000; https://clinicaltrials.gov/ct2/show/NCT04186000.

Examining What We Know in Relation to How We Know It: A Team-Based Reflexivity Model for Rapid Qualitative Health Research.

Reflexivity constitutes a core component of qualitative research and has been actively integrated into long-term and "lone ranger" approaches to qualitative research. However, its application to team-based approaches and particularly to rapid qualitative team-based approaches continues to lag behind. In this article, we introduce a reflexivity model we developed for teams undertaking rapid qualitative studies. Utilizing our most recent application of this model to a rapid qualitative appraisal of health care workers' experiences delivering care during the COVID-19 pandemic as a case study, we identify the steps to put this model into practice and its main outcomes. Our application of the model revealed that the team's practices could be grouped along four dimensions: design assumptions, data collection and analysis processes, multidisciplinary collaboration, and responsible dissemination. Reflexivity can improve the relations within the team and the quality of the research output, if it is implemented as a continuous and iterative process.

Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure.

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.

Sex differences in the effect of diet, obesity, and exercise on bone quality and fracture toughness.

Bone fragility and obesity are both diseases that are multifactorial in etiology and pathology. The contributing role of high fat diet (HFD) versus energy overconsumption on bone health is controversial. Exercise is often prescribed for improving bone health, but it is unclear whether HFD or overconsumption influences skeletal adaptations to exercise. Female and male Wistar rats were fed HFD or low fat diet (LFD) for 10 weeks, starting at 8 weeks of age. Within HFD, rats were labeled Obesity-Resistant (OR) or Obesity-Prone (OP) based on weight and fat gain. Within each diet and phenotype group, rats were randomized to treadmill exercise or sedentary control (SED) for the final 4 weeks. Femurs were assessed for fracture toughness. Cortical lamellar and nonlamellar bone microscale material behavior and chemistry were assessed using nanoindentation and Raman spectroscopy. Female bones had higher fracture toughness and mineral: matrix ratio than male bones. Diet and energy overconsumption affected bone characteristics in a sex-dependent manner, where the divergence between OP and OR in response to HFD occurred more rapidly in males. Diet composition, in general, had a stronger effect on bone quality than overconsumption. HFD dramatically decreased bone size and lamellar mineral:matrix compared to LFD. Effects of short-term exercise training on microscale tissue properties were generally more robust with LFD. Exercise enhanced the contrast between lamellar and nonlamellar bone for nanoindentation modulus but decreased this contrast for plastic work. Our data demonstrate the complexities in the relationship between diet and obesity and highlight the importance of addressing both aspects when characterizing bone quality and fracture resistance.

Perceptions and experiences of healthcare workers during the COVID-19 pandemic in the UK.

OBJECTIVE: The COVID-19 pandemic has set unprecedented demand on the healthcare workforce around the world. The UK has been one of the most affected countries in Europe. The aim of this study was to explore the perceptions and experiences of healthcare workers (HCWs) in relation to COVID-19 and care delivery models implemented to deal with the pandemic in the UK. METHODS: The study was designed as a rapid appraisal combining: (1) a review of UK healthcare policies (n=35 policies), (2) mass media and social media analysis of front-line staff experiences and perceptions (n=101 newspaper articles, n=1 46 000 posts) and (3) in-depth (telephone) interviews with front-line staff (n=30 interviews). The findings from all streams were analysed using framework analysis. RESULTS: Limited personal protective equipment (PPE) and lack of routine testing created anxiety and distress and had a tangible impact on the workforce. When PPE was available, incorrect size and overheating complicated routine work. Lack of training for redeployed staff and the failure to consider the skills of redeployed staff for new areas were identified as problems. Positive aspects of daily work reported by HCWs included solidarity between colleagues, the establishment of well-being support structures and feeling valued by society. CONCLUSION: Our study highlighted the importance of taking into consideration the experiences and concerns of front-line staff during a pandemic. Staff working in the UK during the COVID-19 pandemic advocated clear and consistent guidelines, streamlined testing of HCWs, administration of PPE and acknowledgement of the effects of PPE on routine practice.

Carrying Out Rapid Qualitative Research During a Pandemic: Emerging Lessons From COVID-19.

Social scientists have a robust history of contributing to better understandings of and responses to disease outbreaks. The implementation of qualitative research in the context of infectious epidemics, however, continues to lag behind in the delivery, credibility, and timeliness of findings when compared with other research designs. The purpose of this article is to reflect on our experience of carrying out three research studies (a rapid appraisal, a qualitative study based on interviews, and a mixed-methods survey) aimed at exploring health care delivery in the context of COVID-19. We highlight the importance of qualitative data to inform evidence-based public health responses and provide a way forward to global research teams who wish to implement similar rapid qualitative studies. We reflect on the challenges of setting up research teams, obtaining ethical approval, collecting and analyzing data in real-time and sharing actionable findings.

Rapid Techniques in Qualitative Research: A Critical Review of the Literature.

Qualitative researchers are under increasing time demands to rapidly collect, analyze, and disseminate the results of their findings. Adaptations to qualitative methods may be required to enable the use of timely and relevant qualitative data across multiple disciplinary settings. The aim of this review is to briefly explore the ways in which data collection and analysis methods have been adapted in qualitative research to deal with short study timeframes. We carried out a two-phased systematic review of the literature and determined there were six primary reasons why rapid techniques were used: (a) reduce time, (b) reduce cost, (c) increase the amount of collected data, (d) improve efficiency, (e) improve accuracy, and (f) obtain a closer approximation to the narrated realities of research participants. In addition, we analyzed the characteristics of the articles, how traditional methods were adapted and evaluated, the benefits and limitations of using rapid techniques, and future recommendations.

Compensatory eating behaviors in male and female rats in response to exercise training.

Exercise is often used as a strategy for weight loss maintenance. In preclinical models, we have shown that exercise may be beneficial because it counters the biological drive to regain weight. However, our studies have demonstrated sex differences in the response to exercise in this context. In the present study, we sought to better understand why females and males exhibit different compensatory food eating behaviors in response to regular exercise. Using a forced treadmill exercise paradigm, we measured weight gain, energy expenditure, food intake in real time, and the anorectic effects of leptin. The 4-wk exercise training resulted in reduced weight gain in males and sustained weight gain in females. In male rats, exercise decreased intake, whereas it increased food intake in females. Our results suggest that the anorectic effects of leptin were not responsible for these sex differences in appetite in response to exercise. If these results translate to the human condition, they may reveal important information for the use and application of regular exercise programs.

A strategic approach to social accountability: Bwalo forums within the reproductive maternal and child health accountability ecosystem in Malawi.

BACKGROUND: The majority of documented social accountability initiatives to date have been 'tactical' in nature, employing single-tool, mostly community-based approaches. This article provides lessons from a 'strategic', multi-tool, multi-level social accountability project: UNICEF's 'Social Accountability for Every Woman Every Child' intervention in Malawi. METHODS: The project targeted the national, district and community levels. Three Civil Society Organisations (CSOs) were engaged to carry out interventions using various tools to generate evidence and political advocacy at one or more levels. This article focuses on one of the social accountability methods - the bwalo forum (a meeting based on a traditional Malawian method of dialogue). A detailed political economy analysis was conducted by one of the co-authors using qualitative methods including interviews and group discussions. The authors conducted in-country consultations and analysed secondary data provided by the CSOs. RESULTS: The political economy analysis highlighted several ways in which CSO partners should modify their work plans to be more compatible with the project context. This included shifting the advocacy and support focus, as well as significantly expanding the bwalo forums. Bwalos were found to be an important platform for allowing citizens to engage with duty bearers at the community and district levels, and enabled a number of reproductive, maternal, newborn, child and adolescent health issues to be resolved at those levels. The project also enabled learning around participant responses as intermediate project outcomes. CONCLUSIONS: The project utilised various tools to gather data, elevate community voices, and facilitate engagement between citizen and state actors at the community, district and national levels. This provided the scaffolding for numerous issues to be resolved at the community or district levels, or referred to the national level. Bwalo forums were found to be highly effective as a space for inter-level engagement between citizens and state; however, as they were not embedded in existing local structures, their potential for sustainability and scalability was tenuous. A key strength of the project was the political economy analysis, which provided direction for partners to shape their interventions according to local and national realities and be sensitive to the barriers and drivers to positive action.

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury. METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts. RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury. CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

Proximity-Based Compression for Network Embedding.

Network embedding that encodes structural information of graphs into a low-dimensional vector space has been proven to be essential for network analysis applications, including node classification and community detection. Although recent methods show promising performance for various applications, graph embedding still has some challenges; either the huge size of graphs may hinder a direct application of the existing network embedding method to them, or they suffer compromises in accuracy from locality and noise. In this paper, we propose a novel Network Embedding method, NECL, to generate embedding more efficiently or effectively. Our goal is to answer the following two questions: 1) Does the network Compression significantly boost Learning? 2) Does network compression improve the quality of the representation? For these goals, first, we propose a novel graph compression method based on the neighborhood similarity that compresses the input graph to a smaller graph with incorporating local proximity of its vertices into super-nodes; second, we employ the compressed graph for network embedding instead of the original large graph to bring down the embedding cost and also to capture the global structure of the original graph; third, we refine the embeddings from the compressed graph to the original graph. NECL is a general meta-strategy that improves the efficiency and effectiveness of many state-of-the-art graph embedding algorithms based on node proximity, including DeepWalk, Node2vec, and LINE. Extensive experiments validate the efficiency and effectiveness of our method, which decreases embedding time and improves classification accuracy as evaluated on single and multi-label classification tasks with large real-world graphs.

Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain.

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.

Impact of Exercise and Activity on Weight Regain and Musculoskeletal Health Post-Ovariectomy.

The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high-fat diet (HFD) to reveal obesity-prone (OP) and obesity-resistant (OR) phenotypes. The OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium-fat diet. Rats were then maintained in energy balance for 8 wk before OVX. After OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h·d, 6 d·wk, 15 m·min. Energy intake, spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance pre-OVX, and at three time points post-OVX: before weight regain, during early regain, and after regain. Data are presented as mean ± SE. Exercise attenuated weight regain after OVX in OP only (OP-EX, 123 ± 10 g; OP-SED, 165 ± 12 g; OR-EX, 121 ± 6 g; OR-SED, 116 ± 6 g), which was primarily an attenuation of fat gain. The early post-OVX increase in energy intake explained much of the weight regain, and was similar across groups. Exercising improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to post-OVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA after ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction.

Compensation for cold-induced thermogenesis during weight loss maintenance and regain.

Prevalence of obesity is exacerbated by low rates of successful long-term weight loss maintenance (WLM). In part, relapse from WLM to obesity is due to a reduction in energy expenditure (EE) that persists throughout WLM and relapse. Thus, interventions that increase EE might facilitate WLM. In obese mice that were calorically restricted to reduce body weight by ~20%, we manipulated EE throughout WLM and early relapse using intermittent cold exposure (ICE; 4°C, 90 min/day, 5 days/wk, within the last 3 h of the light cycle). EE, energy intake, and spontaneous physical activity were measured during the obese, WLM, and relapse phases. During WLM and relapse, the ICE group expended more energy during the light cycle because of cold exposure but expended less energy in the dark cycle, which led to no overall difference in total daily EE. The compensation in EE appeared to be mediated by activity, whereby the ICE group was more active during the light cycle because of cold exposure but less active during the dark cycle, which led to no overall effect on total daily activity during WLM and relapse. In brown adipose tissue of relapsing mice, the ICE group had greater mRNA expression of Dio2 and protein expression of UCP1 but lower mRNA expression of Prdm16. In summary, these findings indicate that despite robust increases in EE during cold exposures, ICE is unable to alter total daily EE during WLM or early relapse, likely due to compensatory behaviors in activity.