https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60813-1.pdf

The global obesity pandemic: shaped by global drivers and local environments

https://www.nccor.org/annualreport2013/downloads/Obesity-2.pdf

Health and economic burden of the projected obesity trends in the USA and the UK

Obesity is prevalent in the U.S. population and contributes significantly to morbidity and mortality. Treatments include behavioral therapy, pharmacotherapy, and bariatric surgery. Some sequelae of obesity are reversed with weight loss. Maintaining weight loss is a challenge.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1514009

Mechanisms, Pathophysiology, and Management of Obesity

This article describes the interplay among energy intake, energy expenditure, and body energy stores and illustrates how an understanding of energy balance can help us develop strategies to reduce obesity. First, reducing obesity requires modifying both energy intake and energy expenditure, not simply focusing on either alone. Food restriction alone will not be effective in reducing obesity if human physiology is biased toward achieving energy balance at a high energy flux (ie, at a high level of energy intake and expenditure). In previous environments, a high energy flux was achieved with a high level of physical activity, but in today's sedentary environment, it is increasingly achieved through weight gain. Matching energy intake to a high level of energy expenditure will likely be more feasible for most people than restricting food intake to meet a low level of energy expenditure. Second, from an energy balance point of view, we are likely to be more successful in preventing excessive weight gain than in treating obesity. The reason is that the energy balance system shows stronger opposition to weight loss than to weight gain. Although large behavior changes are needed to produce and maintain reductions in body weight, small behavior changes may be sufficient to prevent excessive weight gain. The concept of energy balance combined with an understanding of how the body achieves balance may be a useful framework for developing strategies to reduce obesity rates.

Obesity is often considered to be a result of either excessive food intake or insufficient physical activity. There is a great debate about which behavior deserves the most responsibility, but this approach has not yet produced effective or innovative solutions. We believe that obesity can best be viewed in terms of energy balance. The first law of thermodynamics states that body weight cannot change if, over a …

Energy Balance and Obesity

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60815-5.pdf

Changing the future of obesity: science, policy, and action

http://www.nccor.org/annualreport2013/downloads/Obesity-3.pdf

Quantification of the effect of energy imbalance on bodyweight

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA (K D Hall PhD, D Chandramohan BSc, C C Chow PhD); WHO Collaborating Centre for Obesity Prevention, Deakin University, Melbourne, VIC, Australia (G Sacks PhD, B A Swinburn MD); Mailman School of Public Health, Columbia University, New York, NY, USA (Y C Wang MD); and Department of Society, Human Development and Health, Harvard School of Public Health, Harvard University, Boston, MA, USA (S L Gortmaker PhD) Obesity 3

Obesity 3 Quantification of the effect of energy inbalance on bodyweight

Whole genome screening is currently not available in preimplantation genetic testing (PGT) due to poor performance of whole genome amplification methods. Here, we present the first validation study using our latest whole genome amplification (WGA) protocol, which yields amplified DNA with comparable quality to genomic DNA when perfoming whole genome sequencing assays. We started by validating PGT for aneuploidy (PGT-A) using our WGA protocol on cell lines and donated human embryos, where amplification success rates were >99.9% and 96.2% respectively. Accuracy on both was >99.9% on aneuploidy status. We next validated whole genome sequencing using amplified and genomic DNA from the Genome in the Bottle reference sample NA12878 to demonstrate accuracy, specificity, sensitivity, and precision of our WGA methods. Amplified DNA and genomic DNA are comparable in this case, with 99.99% accuracy, 99.99% specificity, 98.0% sensitivity and 98.1% precision with our WGA protocol. We additionally examined variant calls between biopsies and the remaining embryos from which they were derived. Again, 99.99% accuracy, 99.99% specificity, 98.1% sensitivity and 98.0% precision were observed. Mitochondrial heteroplasmy between biopsies and embryos was validated, and 99.9% accuracy, 100% specificity, 99.1% sensitivity and 100% precision were observed. Finally, we demonstrated the ability to improve the accuracy of certain types of mendelian variants in our data to close to 100% by leveraging parental and a born child’s genome to perform linkage analysis.

Dhruva Chandramohan

Papers

Quantification of the effect of energy imbalance on bodyweight

Obesity 3 Quantification of the effect of energy inbalance on bodyweight

Validation of the first PGT-whole genome sequencing approach including mitochondrial variants