The Myth of Starving Cells

On the heels of my last post discussing Tom Naughton's novel theory on obesity and blood glucose regulation, I'm reminded again of the whole "fatty acids are locked away in the fat cells" - what I'll call the Starving Cells  Myth - of obesity.  Dr. Eades is weighing in on his blog on Taubes' Why We Get Fat and reiterates once again the fallacy that is the locked away fat.  Here's how he puts it:

... A non-obese person eats, uses the energy from the food and stores the rest. During the time between meals and during sleep, the non-obese person draws on the stored fat to provide energy. When the fat cell mass decreases to a certain critical point, the body signals the brain that the fat cells need a refill, so the brain initiates the hunger response. The non-obese person eats, uses some energy for immediate needs, fills the fat cells with the rest, uses the stored energy as needed, and then the cycle repeats.

It doesn’t work that way in the obese. Obese people eat, use the energy required for immediate needs and store the rest. But–and this is the extremely important ‘but’– during the time between meals and during sleep, obese people can’t access their fat stores because their baseline insulin is too high. When they can’t get to their stored fat, the lack of access to energy sets in motion all the same biochemical signals in the obese person that get sent in the non-obese, who have depleted the energy storage in their fat cells. And these signals are converted by their brains into the drive to feed, i.e., intense hunger. They have to eat to provide for their immediate energy needs because, thanks to chronically elevated insulin levels, they can’t get into to their own stored fat, even though it’s there waiting in massive quantities.

Now this all sounds perfectly reasonable, which is probably why so many just accept this as truth coming from an expert and all.   

After all, just a few paragraphs earlier, Eades makes the following statements:

We now know why we get fat. Excess insulin drives fat into the fat cells increasing the fat cell mass, ultimately leading to the state we call obesity. If we keep walking this progression back, the next question has to be, Why do we make too much insulin?

We make too much insulin because we eat too many carbohydrates, especially sugar and other refined carbohydrates. With that statement, we’re starting to edge into controversial territory, but it’s only territory populated by the ignorant. The hard science is emphatic that carbs are a pure insulin play. Eat them and your insulin goes up....

... carbs increase insulin, excess insulin drives excess fat into the fat cells, the fat cell mass grows, and we become fat. This chain of cause and effect leads to the ineluctable conclusion that excess carbohydrate intake leads to obesity. And each and every link forged in this chain is scientifically unimpeachable.

So if you are fat and want this progression to reverse itself, wouldn’t it make sense to reduce your carbohydrate intake? All the science is valid.

This is an area where I'm going to acknowledge the absolute genius of Gary Taubes.  He's made quite the career citing valid science but then spinning it to convince people that the same science supports his theories.  Only he ignores a large (and growing) body of scientific research that directly contradicts his hypothesis.   See, the science is all there and indisputable on carbohydrates, insulin and fat cell metabolism.  But nobody denies any of the following scientific facts of what happens after a carby meal:

• Carbohydrates stimulate an insulin response
• Insulin favors storage of fats in the fat cells by suppressing lipolysis (HSL) and/or stimulating uptake and esterification.  
• Insulin stimulates glycogen synthesis, de novo lipogenesis, glycolysis
• Insulin suppresses glycogenolysis, gluconeogenesis, and fatty acid oxidation

But it's taking these essentially out of context -- extrapolating short term actions to metabolic behavior over the full 24 hours in a day -- that the problems lie.  So let's return to Dr. Eades' scenarios now.  Lean people apparently do all the things above, but he acknowledges that in between, insulin levels fall favoring release of fatty acids from fat cells, uptake by muscle and other tissues and subsequent "burning" for energy.  He claims that obese people do all of the above, but their insulin never drops low enough to allow for the release.  

Now ... the first question I always have when I hear such theories is how did the lean person's fat cells go rogue in the first place?   There are billions of lean humans on this planet for whom the 151st gram of carbohydrate didn't spark an adipocyte mutiny!   Eades and Taubes and so many others are stuck in the mindset of carbs causing insulin resistance.  They can only do this by ignoring a vast body of peer review research from scientists Taubes has interviewed for his books (though apparently not read much of their work).  I'm talking Keith Frayn and Guenther Boden here.  

But assuming we're en masse participants in a Fat Cells Gone Wild reality show, let's look at what the science says compared to what Dr. Eades "teaches" us.  

Eades:  In most people, the fat cells develop insulin resistance later, which creates the problem. If insulin levels are high to control the liver’s sugar factory output, then these elevated insulin levels are sending a strong message to the non-insulin-resistant fat cells. The message is take this fat and store it. High insulin not only drives fat into the fat cells, it prevents it from getting out. Fat is packed into the fat cells and kept there.

Between meals when insulin levels would normally fall, allowing the liberation of fat to feed all the body’s tissues, insulin remains high in an effort to keep the liver in check. Fat can’t get out of the fat cells, and the tissues begin to starve. Even though there is plenty of stored fat, the body can’t get to it because elevated insulin is preventing its release.

Frayn:  NEFA release from adipose tissue is suppressed by insulin in both lean and obese individuals, but in obesity the process is ‘insulin resistant’ in that the dose–response curve is shifted to the right. NEFA release per unit fat mass is actually less in obese subjects than in lean subjects (effectively, it is down regulated by the fasting hyperinsulinaemia).  However, because of the increased fat mass, total NEFA delivery to the circulation is increased in obesity.  Furthermore, if ‘lean body mass’ (including skeletal muscle and liver) is used as the denominator for NEFA turnover, then NEFA delivery to the consuming tissues is clearly increased in obesity. The ‘insulin resistance’ of adipose tissue lipolysis may be particularly relevant in relation to the delivery of NEFA in the postprandial period.  Despite high plasma insulin concentrations in response to a standard mixed meal, obese subjects fail to suppress NEFA release from adipose tissue at a time when it is completely suppressed in lean subjects.

I've shared quite a bit of material by Keith Frayn and related research groups.  But there are other "research conglomerates" out there.  One of note is Guenther Boden's group at Temple.   Unfortunately most of Boden's body of work finds itself hidden behind pay walls, but I've been lucky to obtain full texts of several of his more comprehensive review articles.   Just one such example includes the following:

...Plasma free fatty acid (FFA) concentrations are commonly elevated in obese individuals [1], most likely due to increased FFA release associated with an expansion in fat mass [2,3]. Elevated plasma FFA are common in type 2 diabetes [4] and early changes may be predictive for the transition of patients from impaired glucose tolerance (IGT) to type 2 diabetes [5,6]. Furthermore, studies indicate that elevated circulating FFA may directly contribute to the underlying pathophysiology of type 2 diabetes, in particular, the development of insulin resistance both in the periphery and the liver [7,8]....

...Over 80% of people with type 2 diabetes are obese, while virtually all are insulin resistant [7]. The association between obesity and insulin resistance is likened to a cause and effect relationship since both human and animal studies indicate that weight loss/gain correlates closely with increasing/decreasing insulin sensitivity, respectively [20–23]. Several factors are proposed to link obesity and insulin resistance and promising candidates include FFA, tumour necrosis factor-α (TNF-α) and leptin. This review will focus on the potential role of FFA while TNF-α and leptin are reviewed elsewhere [24–26].

Adipose tissue has been proposed to be a site of insulin resistance [27]. As insulin resistance develops, there is a decrease in insulin-mediated suppression of lipolysis leading to increased circulating FFA and ultimately insulin resistance in skeletal muscle and liver [7,8]. A strong correlation is observed between increased plasma FFA, intramyocellular lipid accumulation and insulin resistance [28–31]. A number of hypotheses have been put forward to explain the role of FFA and intracellular lipid in the pathogenesis of type 2 diabetes, but, until recently, a more detailed biochemical explanation for FFA-induced insulin resistance has remained elusive.

Like Frayn, Boden seems to favor insulin resistance developing in the fat tissue FIRST, not last, as Eades instructs us.    When this happens, we get in trouble because our cells are not starved, but presented instead with an excess of nutrition.  While cells can refuse glucose to some extent, they seem less able to refuse fatty acids.  While there is a body of evidence that the transport of fatty acids is actively mediated to varying degrees, passive diffusion remains a driving force/factor.  Indeed in the obese, not only are the cells presented with dietary nutrients, but the fat cells are offering up MORE fuel still!  The buildup/backlog/whatever you want to call it in our muscles and organs wreaks havoc on hormonal signaling and metabolism.

Like with Taubes, I had never heard of Eades until after I had lost the bulk of my weight two years ago.  But when I first found his blog liberally cited on discussion forums, I read with interest various older posts that were truly helpful and informative.  Somewhere along the way he wandered off the Reality Reservation where he used to acknowledge the role of calories as in here and here.   I'll not speculate as to why ...