Not enough, rather than too much fat, causes metabolic problems of obesity

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That's right - contrary to what many religiously believe, it is the inability to grow more fat during times of energy surpluss, rather than the excess of fat which appears to directly contribute to the metabolic consequence often associated with obesity.

A recent article in the New Scientist shines some light on this issue;

Obesity kills, everyone knows that. But is it possible that we've been looking at the problem in the wrong way? It seems getting fatter may be part of your body's defense against the worst effects of unhealthy eating, rather than their direct cause.

While the article goes on to discuss some interesting new research, I feel the author misses an opportunity to really challenge the overwhelming dogma that too much fat, per se, is the cause of metabolic consequence of obesity. From my experience, it is much easier to get the point across by investigating the obvious anomalies or outliers to the often thought direct relationship between excess adiposity and disease.

Outlier #1: Lack of adipose tissue leads to severe metabolic abnormalities

Individuals who suffer from a condition called lipodystrophy, have little to no fat tissue (they look extremely athletic, with defined musculature) but display many of the metabolic symptoms thought to be exclusive to obese individuals. Lipodystrophy encompasses a heterogeneous group of disorders associated with whole body or partial lack of adipose tissue, which can be inherited (genetic-origin) or acquired. Not only are patients with lipodystrophy at increased metabolic risk, but the severity of metabolic complications observed is closely related to the extent of their fat loss.

Outlier #2: Excessive growth of adipose tissue leads to healthy metabolic profile

The opposite clinical example of lipodystrophy is multiple symmetric limpomatosis. Multiple symmetric lipomatosis represents a group of similar syndromes characterized by the excessive growth of subcutaneous fat, often in the periphery of the body in areas such as the arms, legs, shoulders, and neck (picture the Michelin man). For a given BMI, multiple symmetric lipomatosis patients are reported to carry 50% more fat tissue than healthy individuals. Interestingly, numerous case studies have found excellent metabolic status (high insulin sensitivity, normal glucose tolerance, normal blood lipid levels and blood pressure) among these individuals despite their obviously obese state.

Outlier #3: Liposuction of adipose tissue does not lead to metabolic improvements

If merely the amount of excess fat is the direct cause of metabolic dysregulation then removing that fat through surgery should obviously result in metabolic improvement. Unfortunately, this is not the case. In fact, an excellent prior study has shown that liposuction does not make obese individuals healthy.

Outlier #4: Pharmacological treatment of unhealthy obese individuals leads to increased adiposity in concert with improvement in metabolic profiles.

All of the above examples would seem to suggest that if obese and metabolically unhealthy individuals could somehow develop more subcutaneous fat tissue, they could theoretically become healthier.

Guess what? That's exactly what happens!

Obese individuals with metabolic problems who are prescribed a class of drugs called thiazolidinediones or TZDs for short, actually grow more fat cells, get fatter, but also get healthier.

Currently, the emerging theory of why obesity is associated with metabolic disease risk suggests that it is not the excess amount of fat that results in problems - but rather, it is the inability of the fat tissue (specifically subcutaneous) to expand enough via the development of numerous, healthy adipocytes or fat cells to store all the excess calories being ingested (more details on that here). 

The mantra that "fat is bad" is not only myopic, it now stands in the face of much contradictory evidence. As the examples above illustrate, matters related to excess fat and health risk are much more nuanced than what many would have you believe.

Finally, while I only discussed issues related to metabolic health, it is also proposed that the association between excess fat and other conditions such as osteoarthritis, sexual dysfunction, and cancer may also be more closely tied to the function rather than merely the amount of fat in one's body. These notions are nicely summed up by Dr. Harold Bays' adiposopathy theory, which has been getting more traction over the years as more supporting evidence emerges (check the reference below). Alas, this may be an issue for a future post.

Have a great weekend.

Peter Janiszewski

Bays, H., & Dujovne, C. (2006). Adiposopathy is a more rational treatment target for metabolic disease than obesity alone Current Atherosclerosis Reports, 8 (2), 144-156 DOI: 10.1007/s11883-006-0052-6

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It was cool to see this release because it totally confirms my biases. ;-)

I still think there's a missing piece in the area of nutrient partitioning, though. I'm not a carb-hater by any means, but I really suspect that carbohydrate intake needs to be kept in proportion to muscle mass and activity level more tightly than other macronutrients...but who knows, really.

Nice article, Peter! If we MUST overconsume, it's better to increase subcutaneous fat than to max out those cells and store it elsewhere, complicating the workings of more metabolic tissues. (Of course the simplest alternative is to consistently achieve energy balance through proper diet and exercise, but we're increasingly looking to surgical and medical alternatives to behavioral problems.) This article summarizes the extremes nicely to highlight your point. Great work!

Damn cool! Thanks!

(I shudder to think how the science media will distort this's far too complicated for them to consider writing about accurately. Alas.)

Thanks Dr.Lance! Great to see you are following the blog:)

You are absolutely right, maintaining energy balance should be the goal, as should healthy eating patterns and attaining adequate physical activity levels. Whenever I discuss such issues, I'm often afraid how what I say may be misconstrued. Quite simply, all I want to get across is that fat tissue is an essential organ that when absent leads to many problems. The all-too-common vilification of fat is misguided; fat tissue is not inherently detrimental, in fact, quite the opposite - it is there to help you buffer energy when available in excess.

Of course, none of this evidence condones weight gain or suggest it is somehow benign. The problem is that we have no control over how our body responds to excess energy - some can easily expand their adipose tissue via growing more healthy fat cells (akin to the multiple symmetric lipomatosis example) while others develop metabolic problems in response to minimal calorie surplus within the normal to overweight BMI ranges as their adipose tissue has a very limited capability for expansion (sort of like partial lipodystrophy, or the metabolically-abnormal normal weight phenotype).

That would be a comforting thought if hauling around this much mass weren't so hard on the remaining structural elements in my legs.

As it is, I'm just going to have to reduce the load factor. Put another way, it ain't the BMI it's the PSI.

By D. C. Sessions (not verified) on 19 Mar 2010 #permalink

The biggest issue RE: obesity seems to be systemic inflammation and insulin resistance, which means there's no doubt that a metabolic dysfunction occurs. Chronic inflammation is problematic on its own, and insulin resistance leads to (and in some regards, results from) all those nasty FFAs constantly circulating in the body.

That almost certainly happens in the central adipostatic systems, but that's a dragon eating it's own tail - in the majority of people, that dysfunction didn't exist before they became fat in the first place. Set point goes up, and it doesn't seem to come back down.

High setpoint means high appetite, which only goes higher as they try to move below that new equilibrium. With an abundance of food, that means a high settling point. Thus the vicious circle.

Thing is, the basics never change - no matter how hard the process gets, mentally or physically, it's always going to boil down to creating an energy deficit, and keeping it up long enough to get the fat off. For the obese, that can take quite awhile.

Hence the quick-fix solutions.

There is an even more basic biochemical advantage of storing fat - efficient storage. When storing fat, adipose tissue is the efficient choice: one gets ~9 Cal/g for consuming fat, whereas only ~4 Cal/g can be derived from stored glucose [glycogen] for amino acids. And fat is hydrophobic, so it can be stored in droplets of pure fat within the cell little excess weight carried along with the stored calories. Glycogen is hydrophilic, so that for every gram of glycogen stored, more than 2 grams of water are also stored.

If you have eaten an excess of 100,000-150,000 Calories over the course of your life, it can be stored in about 12-17 kg. This would be a 60-85 kg person with 20% body fat. If all those excess Calories would be stored as glycogen, you would have to lug around more than 100 kg of stored energy.

By natural cynic (not verified) on 19 Mar 2010 #permalink

This is very very interesting. So if I am one of the 'lucky ones' that can store fat by growing healthy subcutaneous adipose cells then I'm doing OK. But if I'm one of the 'unlucky ones' that stores fat around organs, this affects the normal metabolic processes and leads to disease. Is that right? And if so, my bottom does not count as an organ, right?!

I wonder if the difference in heart disease rates between men and women is related to this.

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