![Professor John Speakman Professor John Speakman](/img/200x200/staffpages/uploads/nhi158/johnbird.jpg)
FRS FMedSci FRSE FRSB FRSA FLS FRSS
Chair in Zoology
- About
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- Email Address
- j.speakman@abdn.ac.uk
- Telephone Number
- +44 (0)1224 272879
- Office Address
- School/Department
- School of Biological Sciences
Biography
For Speakman's biography see the Wikipedia page entry.
External Memberships
Committees
I serve on the following external committees:
Royal Society
- Section 10 medical sciences election committee
- Newton Fund International Fellowships Chairman
- University Research Fellowships (Panel B)
Royal Society of Edinburgh
- Section A3 election committee
Journals
In the last decade I have also served on the editorial boards of the following journals:
- Mammal review 2002 - date
- Aging Cell (section editor) 2004 - 2007
- Journal of Comparative Physiology 2004 - date
- Functional Ecology 2004 - 2009
- Biology letters 2008 - 2013
- Biology Open (deputy editor in chief) 2011 - 2018
- Molecular metabolism (founding board member) 2011 - date
- Science 2011 - date
- IUBMB Life 2012 - date
- Clinical Endocrinology Physiology and Pharmacology 2013 - 2015
- Journal of Genetics and Genomics 2013 - date
- Physiological and Biochemical zoology 2015 - date
- Annals of Human Genetics 2016 - 2019
- International Journal of Obesity 2017 - date
- China Science Life Science 2018 - date
- Philosophical transactions of the Royal Society 2018 - date
- Research
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Research Overview
Over my career so far I have worked on a wide range of topics. Binding them all together is a singular focus on understanding the factors that influence and limit energy expenditure. Since energy is central to all biological processes it provides a common currency for gaining deeper knowledge of the evolutionary forces that have molded animal (including human) adaptations. Early in my career, in the late 1980s and early 1990s, I was instrumental in developing the theoretical and practical basis of an isotope-based methodology for the study of energy demands in free-living animals: called the doubly-labelled water (DLW) technique. In 1997 I published a 400 page book (Doubly-labelled water: theory and practice. Springer New York) which has become the standard reference for the method. This expertise has led my group to become the partner of choice for scientists around the world wishing to apply these techniques in their own studies.
I have used these techniques and the energy balance approach to provide paradigm shifting insights into our understanding of the limits on animal energy expenditure (notably the heat dissipation limits theory), the biology of ageing, and the evolutionary context of the human obesity epidemic (particularly the ‘drifty gene’ hypothesis). These studies have broad implications across many areas of enquiry. A common theme of my work has been to challenge and overturn prevailing ideas with new knowledge gathered from the study of energetics.
Limits to Sustained energy expenditure and intake: I have a long interest in the factors that limit animal expenditure over periods of days and weeks: called sustained energy expenditure (or sustained energy intake – since over such long periods the two must balance). This approach has been used to provide valuable insights in several different areas. In 1998 using the DLW method we showed that African wild dogs have extremely high levels of free-living energy expenditure due mostly to the high costs of hunting (Gorman et al 1998 Nature391: 479-481: front cover). This creates a problem for wild dogs because if their prey is stolen (e.g. by lions or hyenas) the cost of replacing the food becomes extremely expensive. A mathematical model showed that only a slight shift in the level of kleptoparasitism would push the dogs over an energetic precipice to physiologically unsustainable levels of expenditure. This explained why wild dogs are driven to extinction in reserves where large lion and hyena populations are fostered for tourism. It has been widely assumed that this problem would also pertain to cheetah that are similarly kleptoparasitised, and also presumed to have high hunting costs, but work in collaboration with ex-student Michael Scantlebury has suggested otherwise (Scantlebury et al 2014 Science). This is primarily because while cheetah hunts are costly per unit time, they are very short in duration. Hence cheetah have flexibility to sustain much greater levels of kleptoparasitism than wild dogs. At the other end of the metabolic spectrum it has been widely speculated that to survive on their bamboo diet Giant Pandas must have low metabolic rates. We have shown that Panda metabolic rates are among the lowest ever measured in the Eutheria, and can be traced to a panda unique single nucleotide polymorphism in the dual oxidase 2 (DUOX2) gene, which causes a premature stop codon and truncated protein. DUOX2 is critical for thyroid hormone synthesis (Nie et al 2015 Science 349: 171-4).
For most animals breeding is the most energetically expensive period in their lives. They consequently time such effort to match maximal food availability. In some situations this timing may go awry as was observed in populations of blue tits nesting in different habitats in Corsica. Quantification of energy demands using DLW of synchronised and non-synchronised individuals (Thomas et al 2001 Science 291: 2598-2600) showed that desynchronised individuals must work close to their physiological capacity, significantly increasing their mortality rate. This finding has major implications because often the timing of breeding is hard wired into circannual daylight cycles. If the timing of the pulse of maximal food availability changes – for example, due to global climate change, populations may mis-time their breeding events with catastrophic consequences. Elevated ambient temperatures may also have more direct effects on energy expenditure, and this is likely to be particularly important in hibernating animals. Using a mathematical model of hibernal energy balance my group was able to show how climate change will impact the biogeography of bats in North America (Humphries et al 2002 Nature 418: 313-316).
To study this phenomenon of limits in more detail we group have used lactating mice as a model system. Starting in 1996 (Speakman and McQueenie 1996 Physiol. Zool. 69: 746-769) this has led to a series of more than 30 papers mostly in the Journal of Experimental Biology. This work was expanded into a more comprehensive theory concerning the more general limits on animal metabolic rates (the heat dissipation limit theory). The fundamental feature of this revolutionary idea is that endothermic animals are not normally constrained by extrinsic energy supply, but rather are limited by their ability to dissipate body heat, combined with the risk of hyperthermia. This theory was summarised in a landmark paper in 2010 (Speakman and Krol 2010 J. Anim. Ecol. 79: 726-746).
Limits on heat dissipation may have important ramifications as our climate changes. This is because the risk of heatwaves is anticipated to rise in the future. In collaboration with Dr Zhi-Jun Zhao at the university of Wenzhou in China, we have shown in mice and desert hamsters that such changes may have devastating effects paticularly during lactation when there seems to be a critical window of vulnerability to high temperatures (Zhao et al 2020: PNAS).
Energetics and the biology of ageing and life histories. One of the important areas where the heat dissipation limit theory has significant implications is the study of ageing and life histories. In fact ageing, life histories and energetics have a long history of association via the ‘rate of living theory’ which was the first comprehensive theory of ageing, proposed early during the last century. This theory was based on the empirical observation that species with lower rates of metabolism live longer, and found a potential mechanism in the observations that free-radicals are an inevitable by product of oxidative metabolism. The rate of living and free-radical theory of ageing was the dominant theory of ageing until the late 1990s, and the suggested role of free-radicals and oxidative stress as mediators of life history trade-offs has been dominant since that time. My work, (along with many other researchers), has been instrumental in overturning both these ideas. By measuring the energy metabolism of individual mice he showed that it was actually mice with the higher rates of metabolism that lived longest (Speakman et al 2004 Aging cell3: 87-95). I also showed that the links between low metabolism and lifespan are statistical artefacts of not adequately accounting for co-variation due to body size and phylogeny (Speakman, 2005 J. Expt. Biol. 208: 1717-1730.
Energetics and obesity: I have made two distinct contributions to this field. The first is to revolutionise our perceptions of the evolutionary underpinning of the epidemic. Until the mid-2000’s the only evolutionary model for the development of obesity was the ‘thrifty’ gene hypothesis, proposed by Neel in 1962. This suggested that we become obese because in our ancient past deposition of fat provided a safeguard against periods of famine. However, in modern society the system promoting fat storage during periods of plenty results in deposition of excessive amounts of fat in preparation for a famine that never comes: and the result is an obesity epidemic. I have highlighted the many flaws in this superficially attractive idea, and suggested the alternative hypothesis that in our ancient past we were probably very good at regulating our body weight because of the twin threats of starvation and predation. However, 2 million years ago with the invention of fire, weapons and social behaviour we effectively removed the threat of predation: allowing the genes that define our upper body weight control point to drift in time. Because these genes are drifting, rather than being under selection, this explains why everyone does not get fat in modern society. This new idea was elaborated in a breakthrough paper in 2007 (Speakman, 2007 Cell metabolism 6: 5-11) and was subsequently coined the 'drifty' gene hypothesis (Speakman 2008 Int. J. Obesity 32: 1611-1617). This novel approach completely reconceptualises the reasons underpinning the obesity epidemic, and is gathering increasing support from, for example, the GWAS studies of obesity.
My second main contribution to the obesity field is to enter the debate concerning the roles of physical activity and energy expenditure as factors driving the epidemic. In other words, do we eat too much or expend too little (or both). In the 1970 and 1980s it was widely thought that the problem was over-eating, but a highly influential paper by Prentice and Jebb in 1991 suggested the problem was really increasing levels of sedentary behaviour. By the early 2000’s, when I entered this field, it was almost universally believed that reductions in energy expenditure were the main issue. My group published the first data showing that the newly discovered FTO gene (the first GWAS gene linked to obesity) has its effects via modulation of energy intake rather than energy expenditure (Speakman et al 2008 Obesity 16: 1961-1965). This seminal contribution to our understanding of the biological effects of FTO has become the 22nd most cited paper from over 7000 papers published in Obesity over the past 15 years. In collaboration with Klaas Westerterp, we have surveyed data on energy demands dating back to the 1980s. This work showed two things: first that energy expenditure has not declined over this period, and second that the energy demands of humans actually fit very closely to the expected levels of expenditure based on studies of wild animals (Westerterp and Speakman 2008. Int. J. Obesity 32: 1256-1263). This work was an integral part of a turning tide, and now, the idea that the problem with the obesity epidemic is elevated food intake, rather than reduced expenditure, is main stream again.
Current Research
The work of my group currently addresses several key issues with respect to energy balance
1) the role and mechanism by which restriction of calorie intake leads to improved health and lifespan.
This work has been mainly performed in mice and utilised a method of exposing aniamls to graded levels of restriction to elucidate the patterns of change as restriction becomes more intense. Full details of this work can be found on the open science framework pages https://osf.io/9yath. In 2020 I published a revolutionary new idea about why CR has the effects it does - called the 'clean cupboards' hypothesis published in the Naional Science Review
2) The impact of macronutrients on wieght regulation.
There is a long standing debate about the roles played by different macronutrients in weight regulation. We have been working in this field mostly by exposing mice to different macronutrient diets and monitoring their responses in terms of food intake and body weight. A major paper on this work was published in Cell metabolism in 2018. (Hu et al 2018: Cell metabolism).
3) Measuring energy demands of free-living animals and humans using the doubly-labelled water method
4) Exploring the links between fast food consumption and obesity
5) The IAEA doubly-labelled water human database
https://doubly-labelled-water-database.iaea.org/home
- Publications
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Measured energy content of frequently purchased restaurant meals: multi-country cross sectional study
BMJ (Clinical research ed.), vol. 363, k4864Contributions to Journals: ArticlesRegulation of intestinal growth in response to variations in energy supply and demand
Obesity Reviews, vol. 19, no. Suppl 1, pp. 61-72Contributions to Journals: Review articlesLimits to sustained energy intake XXIX: the case of the golden hamster (Mesocricetus auratus)
Journal of Experimental Biology, vol. 221, no. 21, jeb183749Contributions to Journals: ArticlesIt’s eating fat that makes you fat, new mouse study suggests
The ConversationContributions to Specialist Publications: ArticlesDietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice
Cell Metabolism, vol. 28, no. 3, pp. 415-431Contributions to Journals: ArticlesCommunity-wide decline in the occurrence of lesser sandeels Ammodytes marinus in seabird chick diets at a North Sea colony
Marine Ecology Progress Series, vol. 600, pp. 193-206Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.3354/meps12679
- [ONLINE] View publication in Scopus
Response to 'Fat is not just an energy store'
Journal of Experimental Biology, vol. 221, no. 12, jeb184499Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1242/jeb.184499
Association of Fast-Food and Full-Service Restaurant Densities With Mortality From Cardiovascular Disease and Stroke, and the Prevalence of Diabetes Mellitus
Journal of the American Heart Association, vol. 7, no. 11, 007651Contributions to Journals: ArticlesThe effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon
Aging Cell, vol. 17, no. 3, e12746Contributions to Journals: ArticlesBeauty and the Body of the Beholder: Raters' BMI Has Only Limited Association with Ratings of Attractiveness of the Opposite Sex
Obesity, vol. 26, no. 3, pp. 522-530Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1002/oby.22092
Limits to sustained energy intake XXVII: trade-offs between first and second litters in lactating mice support the ecological context hypothesis
Journal of Experimental Biology, vol. 221, no. 5, jeb170902Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1242/jeb.170902
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/12041/1/jeb170902.full.pdf
The evolution of body fatness: trading off disease and predation risk
Journal of Experimental Biology, vol. 221, no. Suppl. 1, jeb167254Contributions to Journals: Review articlesThe Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 73, no. 3, pp. 279-288Contributions to Journals: ArticlesDifferent impacts of resources on opposite sex ratings of physical attractiveness by males and females
Evolution and Human Behavior, vol. 39, no. 2, pp. 220-225Contributions to Journals: ArticlesBiomarker of burden: Feather corticosterone reflects energetic expenditure and allostatic overload in captive waterfowl
Functional Ecology, vol. 32, no. 2, pp. 345-357Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1111/1365-2435.12988
- [ONLINE] View publication in Scopus
On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations
Obesity Reviews, vol. 19, no. 2, pp. 121-149Contributions to Journals: Review articles- [ONLINE] DOI: https://doi.org/10.1111/obr.12625
Reply to VI Kraak
The American Journal of Clinical Nutrition, vol. 107, no. 2, pp. 290-291Contributions to Journals: Comments and Debates- [ONLINE] DOI: https://doi.org/10.1093/ajcn/nqx026
Validation of the doubly labeled water method using off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry
American Journal of Physiology: Endocrinology and Metabolism, vol. 314, no. 2, pp. 124-130Contributions to Journals: ArticlesThe effects of Ramadan fasting on activity and energy expenditure
The American Journal of Clinical Nutrition, vol. 107, no. 1, pp. 54-61Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1093/ajcn/nqx016
Adiposity and Reproductive Cycling Status in Zoo African Elephants
Obesity, vol. 26, no. 1, pp. 103-110Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1002/oby.22123
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/11680/1/elephants_final.docx
- [ONLINE] View publication in Scopus
Why lipostatic set point systems are unlikely to evolve
Molecular Metabolism, vol. 7, pp. 147-154Contributions to Journals: ArticlesEnergy expenditure in professional flat jockeys using doubly labelled water during the racing season: Implications for body weight management
European Journal of Sport Science, vol. 18, no. 2, pp. 235-242Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1080/17461391.2017.1406996
- [ONLINE] View publication in Scopus
GWAS for BMI: a treasure trove of fundamental insights into the genetic basis of obesity
International Journal of Obesity, vol. 42, pp. 1524-1531Contributions to Journals: ArticlesImpact of Obesity and Ozone on the Association Between Particulate Air Pollution and Cardiovascular Disease and Stroke Mortality Among US Adults
Journal of the American Heart Association, vol. 7, no. 11, e008006Contributions to Journals: ArticlesLimits to sustained energy intake XXVIII: Beneficial effects of high dietary fat on lactation performance in mice
Journal of Experimental Biology, vol. 221, jeb180828Contributions to Journals: ArticlesObesity and thermoregulation
Handbook of clinical neurology, vol. 156, pp. 431-443Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/B978-0-444-63912-7.00026-6
Seasonal changes in energy expenditure, body temperature and activity patterns in llamas (Lama glama)
Scientific Reports, vol. 7, pp. 1-12Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1038/s41598-017-07946-7
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/9210/1/s41598_017_07946_7.pdf
The validity of a web-based FFQ assessed by doubly labelled water and multiple 24-h recalls
British Journal of Nutrition, vol. 118, no. 12, pp. 1106-1117Contributions to Journals: ArticlesEnergy balance and the sphingosine-1-phosphate/ceramide axis
Aging, vol. 9, no. 12, pp. 2463-2464Contributions to Journals: Editorials- [ONLINE] DOI: https://doi.org/10.18632/aging.101347
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/9890/1/zzEbzToKopC5bGMkZ.pdf
- [ONLINE] View publication in Scopus
Body macronutrient composition is predicted by lipid and not protein content of the diet
Ecology and Evolution, vol. 7, no. 23, pp. 10056-10065Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1002/ece3.3529
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/9884/1/Moatt_et_al_2017_Ecology_and_Evolution.pdf
- [ONLINE] View publication in Scopus
Response to Farrokhi et al.'s statistical comments on 'no seasonal variation in physical activity of Han Chinese living in Beijing'
The International Journal of Behavioral Nutrition and Physical Activity, vol. 14, pp. 1-2Contributions to Journals: Letters- [ONLINE] DOI: https://doi.org/10.1186/s12966-017-0603-y
- [OPEN ACCESS] http://aura.abdn.ac.uk/bitstream/2164/9721/1/s12966_017_0603_y.pdf
Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo
Molecular Metabolism, vol. 6, no. 10, pp. 1198-1211Contributions to Journals: ArticlesReconstitution of UCP1 using CRISPR/Cas9 in the white adipose tissue of pigs decreases fat deposition and improves thermogenic capacity
PNAS, vol. 114, no. 45, pp. E9474-E9482Contributions to Journals: ArticlesAmbient particulate air pollution (PM2.5) is associated with the ratio of type 2 diabetes to obesity
Scientific Reports, vol. 7, 9144Contributions to Journals: ArticlesHigher densities of fast-food and full-service restaurants are not associated with obesity prevalence
The American Journal of Clinical Nutrition, vol. 106, no. 2, pp. 603-613Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.3945/ajcn.116.151407
The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome
Aging, vol. 9, no. 7, pp. 1770-1824Contributions to Journals: ArticlesWhey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression
American Journal of Physiology: Endocrinology and Metabolism, vol. 313, no. 1, pp. E1-E11Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1152/ajpendo.00356.2016
Energy Intake and Expenditure of Professional Soccer Players of the English Premier League: Evidence of Carbohydrate Periodization
International Journal of Sport Nutrition & Exercise Metabolism, vol. 27, no. 3, pp. 228-238Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1123/ijsnem.2016-0259
The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice
Aging Cell, vol. 16, no. 3, pp. 529-540Contributions to Journals: ArticlesNo seasonal variation in physical activity of Han Chinese living in Beijing
The International Journal of Behavioral Nutrition and Physical Activity, vol. 14, 48Contributions to Journals: ArticlesMechanisms of Action of Surgical Interventions on Weight-Related Diseases: the Potential Role of Bile Acids
Obesity Surgery, vol. 27, no. 3, pp. 826-836Contributions to Journals: Review articles- [ONLINE] DOI: https://doi.org/10.1007/s11695-017-2549-1
- [ONLINE] View publication in Scopus
Metabolic Syndrome Patients Have Lower Levels of Adropin When Compared With Healthy Overweight/Obese and Lean Subjects
American Journal of Men's Health, vol. 11, no. 2, pp. 426-434Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1177/1557988316664074
- [ONLINE] View publication in Scopus
DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue
Cell discovery, vol. 3, 16054Contributions to Journals: ArticlesAccelerometers can measure total and activity-specific energy expenditures in free-ranging marine mammals only if linked to time-activity budgets
Functional Ecology, vol. 31, no. 2, pp. 377–386Contributions to Journals: ArticlesDaily energy expenditure in the face of predation: hedgehog energetics in rural landscapes
Journal of Experimental Biology, vol. 220, no. 3, pp. 460-468Contributions to Journals: ArticlesSex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial
The American Journal of Clinical Nutrition, vol. 105, no. 1, pp. 151-158Contributions to Journals: ArticlesThe effects of graded levels of calorie restriction: VIII. impact of short term calorie and protein restriction on basal metabolic rate in the C57BL/6 mouse
Oncotarget, vol. 8, no. 11, pp. 17453-17474Contributions to Journals: ArticlesCalories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone
Experimental Gerontology, vol. 86, pp. 28-38Contributions to Journals: ArticlesRenal cell carcinoma survival and body mass index: a dose-response meta-analysis reveals another potential paradox within a paradox
International Journal of Obesity, vol. 40, no. 12, pp. 1817-1822Contributions to Journals: Review articles- [ONLINE] DOI: https://doi.org/10.1038/ijo.2016.171
Using doubly-labelled water to measure free-living energy expenditure: Some old things to remember and some new things to consider
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, vol. 202, pp. 3-9Contributions to Journals: Articles- [ONLINE] DOI: https://doi.org/10.1016/j.cbpa.2016.03.017