I think there is not a single, exact answer to this question, as to EXACT mechanism and WHEN this occurs. But I think there is alot of good info out there pointing to the fact that it does occur and that as far as anyone knows, at least some of the resultant changes are very longlasting if not absolutely permanent.
"Yale University researchers have found one of the mechanisms that cause fat cells to lose their ability to efficiently store and use energy - a scientific mystery and a phenomenon that contributes to a major public health problem.
The Yale team discovered a mechanism that allows cellular fat droplets to expand when excess metabolic energy is present - i.e., when the body has taken in more food than it can burn off - helping them to take in fatty acids, the end products of our meals. The obese suffer a myriad of health problems when fat cells can no longer do this job. The scientists report their findings in the Oct. 5 issue of the journal Cell Metabolism. "
The following has been cited by myself and others in other threads, but deserves to be cited ad infinitum, in my book, until who this problem affects is really understood by all, and the extent of the problem and its chronic ramifications are understood.
"But what if we had trouble using fat for energy—or using energy at all? Clearly we’d have a problem: we would eat food, and as soon as the energy was either used or stored, we’d be hungry again—even though we were gaining weight!
This is exactly what happens to many people.
I’ve previously discussed metabolic flexibility and the RER (“Respiratory Exchange Ratio”), also known as the RQ (“Respiratory Quotient”), at length in this article. Metabolic flexibility (“met flex”) is the ability of our cells (specifically, our mitochondria) to switch back and forth between glucose oxidation and fat oxidation for energy, and the RER/RQ is how we measure what proportion of glucose vs. fat we’re burning.
It turns out that:
The obese have impaired metabolic flexibility.
The obese have impaired mitochondrial capacity to turn nutrients into energy in the muscles.
The obese have an impaired ability to oxidize fat for energy, which we can objectively measure.
Both the formerly obese and the soon-to-be-obese also suffer these impairments."
Of great import here is this statement, which I think cannot be repeated and emphasized enough:
"BOTH the FORMERLY OBESE and the SOON-TO-BE-OBESE also suffer from these imapirments."
And of course, the import of the following statement is HUGE:
"In other words, obese people have a greatly decreased ability to create energy from the nutrients they ingest.
The ability to oxidize fat is also impaired. How great is this impairment?"
There are a number of studies that are utilized here and they are all available as links for readers who really want to understand the basis for these statements, and they are all here:
Scroll down to: Satiety Failure #3: Energy Stuck in Storage
Here's a quote from the abstract of a paper which for me, best pulls it all together. The full text version of the research is available in a PDF link on the link page supplied below.
"To develop an explanation for this apparent contradiction in energy homeostasis and the chronic overeating relative to energy used in obesity, a review of the literature was conducted. The resulting model of obesity is based on a growing body of research demonstrating that altered mitochondrial energy production, particularly in skeletal muscles, is a major anomaly capable of setting off a chain of metabolic events leading to obesity. Alterations in skeletal muscle mitochondria distribution and their oxidative and glycolytic energy capacities in obesity are described. The metabolic responses of obese and normal individuals to exercise are contrasted, and the effects of weight loss on energy production are presented. The effect of altered fat oxidation is considered in relation to energy regulation by the central nervous system and the development of major obesity comorbidities, including systemic inflammation, insulin resistance and diabetes, and cardiovascular disease."
Even as much attention (and rightfully so!) has been given to J.Stanton's excellent satiety series, I have not seen any real discussion of the following paper, which I think it a HUGE piece of the puzzle for some of us, and I am one of them for sure!
"They came to the laboratory on two separate days to consume breakfast; on one day the principle energy source was fat and on the other day carbohydrate. Satiety responses were determined by ratings of hunger and fullness for 2 h after breakfast, and intake at a mid-morning snack test. Those scoring high on the TFEQ-disinhibition scale consumed more energy at the snack test than those with low TFEQ-disinhibition, but this was only following the high carbohydrate breakfast. The TFEQ-restraint scale did not independently predict food intake or interact with the TFEQ-disinhibition related overeating. In normal-weight females the tendency to overeat may be related to insensitivity to the satiating effects of carbohydrate."
For me, this research is highly suggestive of a*key* issue for some of us, which I "secretly" hypothesize may worsen over time...that of carbohydrates NOT being satiating for some subset of people. This is absolutely true of me. And the consequences of this are great...REAL HUNGER which occurs too often and too quickly after a "normally" carbohydrate laden meal.
We have to get to the point where we really understand that for one group of people, carbohydrates are satiating and indeed, make them feel "good." And in another group of people, this is absolutely the opposite and will cause real metabolic issues if the macronutrient ratios of meals are too high in carbohydrates.
For now, I think this is enough to chew on...and as my computer is acting up, I will not go into more. Arya Sharma's work should certainly be considrered and I amy provide some links later.
I also feel that we need to be careful about separating the specifice medical diagnosis of metaboic syndrome that some of the obese suffer with, from the larger and different metaboic changes cascade we are talking about here which is a much larger and perhpas more generalized phenomenon among the soon to be obese, obese and formerly obese.
EDIT: OK, at the rsik of making this waaay too long, I cannot leave out Dr. Sharma and a link that so well addresses the question, though, of course, not absolutely definitively. There is no one on earth, right now, who can do that. So, let me just lift a few quotes and supply the link for those who really might give a hoot...
"As readers will recall, the biology of the post-weight loss state is nothing like the biology of someone who has never lost weight. There are countless ways in which the psychoneurobiology, energy physiology and metabolism in anyone who has lost weight are remarkably different from someone ‘naturally’ of that weight."
"The consistent finding from all such studies is that all individuals or animals in a post-weight-loss state face considerable ‘homeostatic pressure’ that aims to drive their weight back to initial levels.
The paper extensively discusses how changes in biological signals of fat stores (e.g. leptin) elicit profound metabolic and behavioural adaptations - a topic that I dealt with extensively in previous posts.
The key findings of increased hunger and appetite, reduced satiety and substantially increased ‘fuel efficiency’ have very real underlying biological drivers - drivers powerful enough to ultimately wear down even the most persistent dieter."
"The paper also extensively discusses some of the lesser known metabolic adaptations to weight loss including profound changes in gut biology that enhance caloric extraction from food as well as alterations in liver function, skeletal muscle and fat tissue that promote weight regain."