Ep. 22: John Speakman—What Causes Obesity?

Tucker Goodrich: Debugging Life

Introduction

I am honored to be joined by John Speakman, a leading authority on energy balance in animals, and in the use of the doubly-labeled water method of determining energy balance. This has led him into the study of obesity, among other topics, where he has become a recognized expert.

Our discussion was prompted by his recent paper, “Total Daily Energy Expenditure Has Declined Over the Past Three Decades Due to Declining Basal Expenditure, Not Reduced Activity Expenditure”, which casts a new light onto the world pandemic of obesity.

In addition to discussing a few of the papers that give some background to that one, and his future research plans in light of that paper, we have an enlightening discussion on the potential role of deuterium in obesity and chronic disease.

Biography:

“John Roger Speakman (born 1958) FRS FRSE FRSB FRSA FMedSci FRSS is a British biologist working at the University of Aberdeen, Institute of Biological and Environmental Sciences, for which he was Director from 2007 to 2011. He leads the University's Energetics Research Group, which is one of the world's leading groups using doubly labeled water (DLW) to investigate energy expenditure and balance in animals. Between 2011-2020, he was a '1000 talents' Professor at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, in Beijing, China, where he ran the molecular energetics group. In 2020 he moved to the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences in Shenzhen, China where he works at the Center for Energy Metabolism and Reproduction and Head of the Shenzhen Key laboratory of Metabolic Health.”

https://en.wikipedia.org/wiki/John_Speakman

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Tucker Goodrich

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Show Notes

Hu, S., Wang, L., Yang, D., Li, L., Togo, J., Wu, Y., Liu, Q., Li, B., Li, M., Wang, G., Zhang, X., Niu, C., Li, J., Xu, Y., Couper, E., Whittington-Davies, A., Mazidi, M., Luo, L., Wang, S., … Speakman, J. R. (2018). Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. Cell Metabolism, 28(3), 415-431.e4.

https://doi.org/10.1016/j.cmet.2018.06.010

Wu, Y., Li, B., Li, L., Mitchell, S. E., Green, C. L., D’Agostino, G., Wang, G., Wang, L., Li, M., Li, J., Niu, C., Jin, Z., Wang, A., Zheng, Y., Douglas, A., & Speakman, J. R. (2021). Very-Low-Protein Diets Lead to Reduced Food Intake and Weight Loss, Linked to Inhibition of Hypothalamic Mtor Signaling, in Mice. Cell Metabolism, 33(6), 1264–1266.

https://doi.org/10.1016/j.cmet.2021.04.016

McNay, D. E. G., & Speakman, J. R. (2013). High Fat Diet Causes Rebound Weight Gain. Molecular Metabolism, 2(2), 103–108.

https://doi.org/10.1016/j.molmet.2012.10.003

Speakman, J. R., De Jong, J. M. A., Sinha, S., Westerterp, K. R., Yamada, Y., Sagayama, H., Ainslie, P. N., Anderson, L. J., Arab, L., Bedu-Addo, K., Blanc, S., Bonomi, A. G., Bovet, P., Brage, S., Buchowski, M. S., Butte, N. F., Camps, S. G. J. A., Cooper, J. A., Cooper, R., … Wong, W. W. (2023). Total Daily Energy Expenditure Has Declined Over the Past Three Decades Due to Declining Basal Expenditure, Not Reduced Activity Expenditure. Nature Metabolism, 5(4), 579–588.

https://doi.org/10.1038/s42255-023-00782-2

Gurven, M., Kraft, T. S., Alami, S., Adrian, J. C., Linares, E. C., Cummings, D., Rodriguez, D. E., Hooper, P. L., Jaeggi, A. V., Gutierrez, R. Q., Suarez, I. M., Seabright, E., Kaplan, H., Stieglitz, J., & Trumble, B. (n.d.). Rapidly Declining Body Temperature in a Tropical Human Population. Science Advances, 6(44), eabc6599.

https://doi.org/10.1126/sciadv.abc6599

Protsiv, M., Ley, C., Lankester, J., Hastie, T., & Parsonnet, J. (2020). Decreasing Human Body Temperature in the United States Since the Industrial Revolution. eLife, 9, e49555.

https://doi.org/10.7554/eLife.49555

Linares, C., & Su, D. (2005). Body Mass Index and Health Among Union Army Veterans: 1891–1905. Economics & Human Biology, 3(3), 367–387.

https://doi.org/10.1016/j.ehb.2005.06.002

Sørensen, T. I. A., Martinez, A. R., & Jørgensen, T. S. H. (2022). Epidemiology of Obesity. In J. Eckel & K. Clément (Eds.), From Obesity to Diabetes (pp. 3–27). Springer International Publishing.

https://doi.org/10.1007/164_2022_581

Schramm, S., Sørensen, T. I. A., Davidsen, M., & Tolstrup, J. S. (2023). Changes in Adult Obesity Prevalence in Denmark, 1987–2021: Age–Period–Cohort Analysis of Nationally Representative Data. European Journal of Public Health, 33(3), 463–467.

https://doi.org/10.1093/eurpub/ckad024

Haggerty, C., Hoggard, N., Brown, D. S., Clapham, J. C., & Speakman, J. R. (2008). Intra-Specific Variation in Resting Metabolic Rate in Mf1 Mice Is Not Associated with Membrane Lipid Desaturation in the Liver. Mechanisms of Ageing and Development, 129(3), 129–137.

https://doi.org/10.1016/j.mad.2007.11.001

Zhang, L.-N., Gamo, Y., Sinclair, R., Mitchell, S. E., Morgan, D. G., Clapham, J. C., & Speakman, J. R. (2012). Effects of Chronic Oral Rimonabant Administration on Energy Budgets of Diet-Induced Obese C57BL/6 Mice. Obesity, 20(5), 954–962.

https://doi.org/10.1038/oby.2011.357

“There were four suicides in the rimonabant group (0·07%) and one in the placebo group (0·02%). The number of deaths for bariatric surgery, a widely used alternative treatment for severe obesity, would have been expected to be far greater, and in centres of excellence has been reported to be 0·3% at 90 days.2”

Topol, E. J., Bousser, M.-G., Fox, K. A., & Montelescot, G. (2010). Termination of the CRESCENDO trial – Authors’ reply. The Lancet, 376(9757), 1984–1985.

https://doi.org/10.1016/S0140-6736(10)62256-8

Else, P. L., & Hulbert, A. J. (1987). Evolution of Mammalian Endothermic Metabolism: “Leaky” Membranes as a Source of Heat. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 253(1), R1–R7.

https://doi.org/10.1152/ajpregu.1987.253.1.R1

Speakman, J. R., Sørensen, T. I. A., Hall, K. D., & Allison, D. B. (2023). Unanswered Questions About the Causes of Obesity. Science, 381(6661), 944–946.

https://doi.org/10.1126/science.adg2718

Deuterium

Boros, L., Collins, Q., & Somlyai, G. (2018, September 24). Deuterium and Metabolic Water Matter – What This Means Biochemically and Clinically. https://www.science.org/doi/10.1126/sciadv.aat7314#elettersSection

If you have any questions about sources for things discussed please ask in the comments.