When Weight Impacts Health

[Eddy Edson]

A nice overview from the New England Journal of Medicine.

In this short video for patients and families from the New England Journal of Medicine, experts discuss the current understanding of obesity and explore the surgical and medical therapies for weight loss, with a focus on new, effective treatments. Patients also share their experiences with bias and stigma and their reflections on living with obesity.

 

[Eddy Edson]

A couple of not very important little nitpicks, fwiw:

- The "set point" concept seems to be another just-so explainer story without evidence to support it. See in particular John Speakman's critiques & alternatives:

https://twitter.com/x/status/1493584628422258693

- I don't think the notion that the healthiest BMI is around the top end of "healthy" / bottom end of "overweight" is very well supported? The studies I've seen which suggest this are vulnerable to reverse-causation questions.

 

[Eddy Edson]

Another piece on "dual intervention point" versus "set point" hypotheses from John Speakman's group, looking at obesity from an evolutionary perspective: https://academic.oup.com/lifemeta/article/1/1/10/6575876

People completely lacking body fat (lipodystrophy/lipoatrophy) and those with severe obesity both show profound metabolic and other health issues. Regulating levels of body fat somewhere between these limits would, therefore, appear to be adaptive.

Two different models might be contemplated. More traditional is a set point (SP) where the levels are regulated around a fixed level. Alternatively, dual-intervention point (DIP) is a system that tolerates fairly wide variation but is activated when critically high or low levels are breached.

The DIP system seems to fit our experience much better than an SP, and models suggest that it is more likely to have evolved.

A DIP system may have evolved because of two contrasting selection pressures. At the lower end, we may have been selected to avoid low levels of fat as a buffer against starvation, to avoid disease-induced anorexia, and to support reproduction. At the upper end, we may have been selected to avoid excess storage because of the elevated risks of predation. This upper limit of control seems to have malfunctioned because some of us deposit large fat stores, with important negative health effects.

Why has evolution not protected us against this problem? One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary history. By chance, it fell apart more in some people than others, and these people are now unable to effectively manage their weight in the face of the modern food glut.

To understand the evolutionary context of obesity, it is important to separate the adaptive reason for storing some fat (i.e. the lower intervention point), from the nonadaptive reason for storing lots of fat (a broken upper intervention point). The DIP model has several consequences, showing how we understand the obesity problem and what happens when we attempt to treat it.

 

[everydayupsanddowns]

It has made sense to me for a while, that given the relative scarcity of food, and the hardness of life throughout much of human history, that those that survived were probably likely to be the ones who had a better innate ability to lay down fat stores when food was actually available.

Except that now food is always available, in huge quantities. And an advertising / marketing / food industry / economic growth / prosperity environment since the second world war has hugely increased the sociological ‘pressure’ (or at least opportunity) to make every moment of every day a chance to consume.

Nothing more than a hunch really, but it fits the pattern that I see around me.

 

[Eddy Edson]

It has made sense to me for a while, that given the relative scarcity of food, and the hardness of life throughout much of human history, that those that survived were probably likely to be the ones who had a better innate ability to lay down fat stores when food was actually available.

It's interesting to read what Speakman et al have to say about that model, and alternatives to it:

Perhaps, the earliest idea about fat storage (and hence an evolutionary model of obesity) is that it evolved as a buffer against failures in the environmental food supply. This idea is commonly known as the Thrifty gene hypothesis or TGH [82] ...

The TGH is that humans have always been living in an environment characterized by sparse and unpredictable food supplies. Hence, it was argued that when food supplies failed it would have been those individuals who stored more fat would have had a greater chance of survival. This means that the genes favoring fat storage were positively selected.... As noted elsewhere, this is an intuitively attractive model [83], but it has almost no supportive evidence, and there is considerable evidence against it. ... Yet, despite this overwhelming evidence, it refuses to die [85], and the original paper has already been cited more than 2000 times.

The problems with the TGH have been elaborated elsewhere [9, 83, 86–90] but will be briefly summarized and added to here. The first issue is that there is no evidence to support the suggestion that we have always been inhabited a niche characterized by low and intermittent food supply. Indeed, in some scenarios, pre-agricultural hominids (e.g. Homo erectus) were an apex predator that was awash with abundant energy supplies from the vast African populations of large mega-herbivores such as elephants [91, 92]. Moreover, early hominids and early populations of Homo sapiens have been characterized as driving the extinction of these prey items because they killed many more than were needed for food—the overkill hypothesis [93, 94]. Overkill is mutually incompatible with the idea of perpetual food shortage. Moreover, once hominids discovered fire, it became possible to cook food items and this greatly increased the energy that could be obtained from plant sources [95]. By this scenario, food shortages probably only started to affect humans once elephants and other mega-herbivores [96] had been extirpated. This led ancestral humans to rely on smaller and smaller prey and an increasingly large diversity of plant and other food sources such as honey [92] until the agricultural revolution. Once humans developed agriculture 8–10k years ago, this did not stabilize the food supply and make it more predictable, but rather famine started to become a more-regular feature of human existence. Food security is higher in hunter–gatherers than subsistence agriculturalists [97]. Moreover, much larger historical populations became highly susceptible to crop failures and unpredictable weather events [98–100].

So, the idea of thrifty genes promoting survival through famines only makes sense in the period since we developed agriculture [100]. Although there are several examples of genetic selection acting over the period since animals were domesticated (e.g. in the lactase gene [101]), the problem with the famine-based selection acting only in the agricultural era is that 10k years is insufficient time for famines to act as a strong selective force on genetic variants influencing fat storage, because catastrophic famine events are relatively rare (every 150 years or so) [86]. More critically for the TGH, however, there is no evidence that the people who survive famines are any fatter than those who die.

...

While catastrophic failure of the food supply or seasonal declines in food is unlikely drivers of fat storage, it is still possible that fat evolved as a buffer against food shortage. This is because at the individual level a person may encounter situations that affect their ability to feed, despite there being abundant food resources available for everyone else. The main factor having this effect is infection with disease [90]. Disease often leads to suppression of hunger called “disease-induced anorexia.” This effect is probably adaptive. A person who is sick may not be effective at gathering food or hunting and may hasten their own demise if they do so, because they burn through their energy faster. Moreover, if debilitated by illness, they may themselves become prey to other animals. Hence, fat may be a buffer to protect against such periods of illness. Modern-day humans have these same physiological responses to infection, and there is lots of evidence that individuals with higher BMI can better survive infectious disease [127–129].

...

It has been noted that humans store considerably more fat than the great apes [145], and this difference is potentially a consequence of the greater risk of contracting infectious diseases in humans because of their greater sociality and living in larger groups.

Another potential use of stored body fat is in anticipation of elevated energy demands, rather than energy shortfalls. For example, fat is stored by migrating birds prior to migration [146]. Many animals also deposit fat stores in anticipation of reproduction, which is also a period of high energy requirements. Indeed, there is a distinction made between animals that predominantly rely on such reserves (like pinnipeds) called “capital breeders” and animals that predominantly utilize elevated intake to fuel reproduction such as mice [147] called “income breeders.” There is substantial evidence to suggest a close link between fat reserves and reproductive function in females which is mediated via circulating leptin levels. The ob/ob mouse, for example, is infertile, but reproductive function can be regained by exogenous provision of leptin [148]. Females with low levels of body fat become amenorrheic [149, 150]. It is noteworthy that the levels of body fat in nonobese individuals of the same BMI are much higher in females than males pointing to support of reproduction as an important driver of these baseline levels of adiposity.

 

[nonethewiser]

You must have great scientific mind to make sense of all that Eddy.

 

[Eddy Edson]

You must have great scientific mind to make sense of all that Eddy.

I just got interested in this stuff.

 

[bulkbiker]

Except that now food is always available, in huge quantities.

And of lot of it is of exceedingly poor quality being stuffed with cheap, long lasting carbohydrate and toxic seed oils.

 

[Eddy Edson]

And of lot of it is of exceedingly poor quality being stuffed with cheap, long lasting carbohydrate and toxic seed oils.

Lol "toxic seed oils" ...

 

[everydayupsanddowns]

So, the idea of thrifty genes promoting survival through famines only makes sense in the period since we developed agriculture [100]. Although there are several examples of genetic selection acting over the period since animals were domesticated (e.g. in the lactase gene [101]), the problem with the famine-based selection acting only in the agricultural era is that 10k years is insufficient time for famines to act as a strong selective force on genetic variants influencing fat storage, because catastrophic famine events are relatively rare (every 150 years or so) [86]. More critically for the TGH, however, there is no evidence that the people who survive famines are any fatter than those who die.

...

While catastrophic failure of the food supply or seasonal declines in food is unlikely drivers of fat storage, it is still possible that fat evolved as a buffer against food shortage. This is because at the individual level a person may encounter situations that affect their ability to feed, despite there being abundant food resources available for everyone else. The main factor having this effect is infection with disease [90]. Disease often leads to suppression of hunger called “disease-induced anorexia.” This effect is probably adaptive. A person who is sick may not be effective at gathering food or hunting and may hasten their own demise if they do so, because they burn through their energy faster. Moreover, if debilitated by illness, they may themselves become prey to other animals. Hence, fat may be a buffer to protect against such periods of illness. Modern-day humans have these same physiological responses to infection, and there is lots of evidence that individuals with higher BMI can better survive infectious disease [127–129].

Interestingly it was more the hard years and poverty post-nomadic that I was thinking of. When we were all much shorter, and making it to 30 or 40 was a pretty good innings.

Interesting that 10,000 years isn’t long enough to do much with selection - even when we were dying like flies!

 

[42istheanswer]

Interestingly it was more the hard years and poverty post-nomadic that I was thinking of. When we were all much shorter, and making it to 30 or 40 was a pretty good innings.

Interesting that 10,000 years isn’t long enough to do much with selection - even when we were dying like flies!

yes, I have come across the idea that it was actively selected for during those times - that particularly for poorer men fatness was seen as attractive in a woman, with the idea that if she could feed herself in hard times then she could feed you and your children better. I'm not sure what data was behind that idea though.

The optimal BMI range for conception for a woman is slightly higher than the oft-quoted healthy range for BMI, but then again women in famine torn countries manage to conceive and feed children (and produce good quality breastmilk in most cases - often it is when children get to the age where breastmilk is no longer an adequate sole source of nutrition that they start to show the malnutrition of famine. I remember those famine videos of the late 80s and early 90s showing apparently healthy looking babies, then as they became toddlers there were the thin arms and swollen bellies of kwashiorkor)

 

[Leadinglights]

yes, I have come across the idea that it was actively selected for during those times - that particularly for poorer men fatness was seen as attractive in a woman, with the idea that if she could feed herself in hard times then she could feed you and your children better. I'm not sure what data was behind that idea though.

The optimal BMI range for conception for a woman is slightly higher than the oft-quoted healthy range for BMI, but then again women in famine torn countries manage to conceive and feed children (and produce good quality breastmilk in most cases - often it is when children get to the age where breastmilk is no longer an adequate sole source of nutrition that they start to show the malnutrition of famine. I remember those famine videos of the late 80s and early 90s showing apparently healthy looking babies, then as they became toddlers there were the thin arms and swollen bellies of kwashiorkor)

As a kid, it was said if I didn't want to eat my food, think of all the starving children in Biafra. Sadly those heart breaking images are not a thing of the past.

 

[Deleted member 21371]

As a kid, it was said if I didn't want to eat my food, think of all the starving children in Biafra. Sadly those heart breaking images are not a thing of the past.

I think it's sad that some western diets (and I mean the short term weightloss diets) get bandied about as "starvation" diets, and how you can't lose weight on them.

Those images show what a starvation diet really is, and should be a thing of the past in a modern world.