History of Food Restriction in Obesity-Prone Animals Confers Survival Advantage

Yesterday, I posted about the observations that the same genes that confer athletic ability by increasing ‘fuel efficiency’ may also promote obesity when such activity ceases. This is in line with the ‘thrifty gene’ hypothesis, that obesity is the ‘natural’ response to genes that conferred survival advantages in our ancestors in the face of famines and increased demands on physical activity.

Interestingly, a study by Abdoulaye Diane and colleagues from the University of Alberta, just published in OBESITY, demonstrates that genetically obesity-prone animals, do in fact have a considerable survival advantage over lean-prone animals, an advantage that is further enhanced, when such animals have previously experienced caloric restriction.

The researchers took advantage of the fact that limiting access to food in mice (by restricting feeding hours) leads to an incremental increase in ‘voluntary’ wheel running associated with reduced food consumption (activity-induced anorexia) and even more running till the animals ultimately exhaust themselves and die.

In their experiments, while food restriction resulted in increased wheel running and reduced food intake in both obesity-prone and lean-prone juvenile mice, the former survived almost twice as long and lost far less of their body weight (percent and absolute values) than the lean-prone mice, which rapidly succumbed to the challenge.

Furthermore, even obesity-prone rats, who were kept lean by restricting their food to the levels of the lean-prone rats (by ‘pair-feeding’), lived longer, suggesting that this was not an advantage conferred simply by greater ‘caloric reserves’.

Interestingly, obesity-prone juvenile mice, who had previously undergone food restriction and regained their weight prior to the challenge, did even better.

Thus, not only was there a clear survival advantage in the genetically obese-prone mice but previous food restriction appeared to confer even more ‘resistance’ to the challenge.

It appear that not only do ‘obesity-prone’ genes allow animals to better cope with the dual challenge of starvation and increased physical activity, but that this ‘metabolic’ prowess can be further enhanced by prior experience with food restriction (weight loss).

Translated to humans, this later finding would suggest that ‘dieting’ makes you even more fuel efficient (which may well explain why dieting increases the risk of subsequent weight gain).

Or as the authors discuss:

“Our results show that juvenile obese-prone rats gain a survival advantage over lean-prone under famine-like conditions, and this advantage is further enhanced by physiological and behavioral changes induced by prior food restriction. In the wild, this survival advantage in young animals, that are the future breeders, would confer increased reproductive success. At a basic level, these results support the “thrifty gene” hypothesis of obesity.”

The authors further conclude:

“Thus, caloric restriction at early ages may predispose obese-prone individuals to become more metabolically efficient. An inducible increase in metabolic efficiency may help to explain the increased obesity in low- and middle-income countries where childhood under-nutrition exists in the context of rapid economic development and rural/urban migration. Thus, the obese-prone phenotype, that is highly deleterious in a food-rich environment, confers a real survival benefit in an unstable and scarce food environment, that is enhanced by prior caloric restriction.”

In summary, if these findings are indeed transferable to humans, they would have several important implications:

1) Genetically obese-prone individuals are better equipped to survive times of scarcity and/or increase physical demand.

2) This ‘survival’ advantage can be further enhanced by previous exposure to caloric restriction (weight loss).

While these findings may also explain the ‘survival paradox’ of obesity, where obese humans with chronic illnesses tend to live longer than skinny people with those illnesses, they also suggest an explanation for why dieting can make you fat.

I certainly do not envy the folks, who have to translate these findings into coherent ‘public health’ recommendations:

a) having genes that promote obesity is actually a survival benefit (if you should happen to encounter a famine)

b) if you are lucky enough to have these obesity genes, you can further increase your survival benefit (to famines) by (periodically?) losing weight

c) however, if you do (periodically?) lose weight, you may also end up getting even more obese – which, although a survival benefit during the next famine, will increase your risk for obesity-related health problems (in case the famine does not come).

I guess you can’t have it all.

AMS
Calgary, Alberta

Diane A, Pierce WD, Heth CD, Russell JC, Richard D, & Proctor SD (2011). Feeding History and Obese-Prone Genotype Increase Survival of Rats Exposed to a Challenge of Food Restriction and Wheel Running. Obesity (Silver Spring, Md.) PMID: 22016097