Weight gain indicates a positive energy balance, with calorie intake exceeding expenditure. However, this fact of physics cannot inform causality. Potential pathways to obesity include a positive energy balance that drives weight gain or weight gain that drives the positive energy balance. Here, we propose an integrated model of obesity pathogenesis that incorporates both pathways.
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References
Sørensen, T. I. A. Challenges in the study of causation of obesity. Proc. Nutr. Soc. 68, 43–54 (2009).
Schwartz, M. W. et al. Obesity pathogenesis: an endocrine society scientific statement. Endocr. Rev. 38, 267–296 (2017).
Hill, J. O. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr. Rev. 27, 750–761 (2006).
Roberts, S. B. et al. Energy expenditure and subsequent nutrient intakes in overfed young men. Am. J. Physiol. 259, R461–R469 (1990).
Friedman, M. I. Fuel partitioning and food intake. Am. J. Clin. Nutr. 67, 513S–518S (1998).
Lustig, R. H. Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics. Nat. Clin. Pract. Endocrinol. Metab. 2, 447–458 (2006).
Ludwig, D. S. et al. The carbohydrate–insulin model: a physiological perspective on the obesity pandemic. Am. J. Clin. Nutr. 114, 1873–1885 (2021).
Pawlak, D. B., Kushner, J. A. & Ludwig, D. S. Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals. Lancet 364, 778–785 (2004).
Hjorth, M. F., Zohar, Y., Hill, J. O. & Astrup, A. Personalized dietary management of overweight and obesity based on measures of insulin and glucose. Annu. Rev. Nutr. 38, 245–272 (2018).
Malik, V. S., Schulze, M. B. & Hu, F. B. Intake of sugar-sweetened beverages and weight gain: a systematic review. Am. J. Clin. Nutr. 84, 274–288 (2006).
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D.S.L. received royalties for books that recommend a carbohydrate-modified diet; his spouse owns a nutrition education and consulting business. T.I.A.S. declares no competing interests.
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Ludwig, D.S., Sørensen, T.I.A. An integrated model of obesity pathogenesis that revisits causal direction. Nat Rev Endocrinol 18, 261–262 (2022). https://doi.org/10.1038/s41574-022-00635-0
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DOI: https://doi.org/10.1038/s41574-022-00635-0