For those who want to understand why, keep reading (hopefully this is still everyone). This topic is — surprise, surprise — very nuanced, and almost always bastardized when oversimplified, which I’m about to do, though hopefully less than most. In part III (and possibly a part IV) of that series, I’ll go more into the actions of ketones and why you may or may not want to consider putting yourself into a state where your liver makes them. There seems to be great confusion around . But, before I try to dispel any of the confusion, we need to go through a little primer on what I like to call “fat flux.”One point before diving in, please do not assume because I’m writing this post that I think adiposity (the technical term for relative amount of fat in the body) is the most important thing to worry about. While there is a correlation between high adiposity (excessive fat) and metabolic dysfunction, that correlation is far from perfect, and, as I’ve discussed elsewhere, I think the arrow of causation goes from metabolic dysfunction to adiposity, not the reverse. In other words, the number of adipocytes (fat cells) we have as an adult does not change nearly as much as their size and fat content. Fat flux 1. 01. According to “An Etymological Dictionary of Modern English,” the word flux comes from the Latin word fluxus and fluere, which mean “flow” and “to flow,” respectively. While the term has a clear mathematical meaning in physics, defined by a dot product I promise I won’t speak of, you can think of flux as the net throughput which takes into account positive and negative accumulation. If we start with a bucket of water and put a hole in the bottom, the result, needless to say, is an efflux of water, or negative water flux. Since TAG are too big to bring across cell membranes, they need to be “hydrolyzed” first into free fatty acids, then re- assembled (re- esterified) back into TAG. Translocates GLUT4 transporters to the plasma membrane from endosomes within the cell. Once bound to albumin the free fatty acids are free to travel elsewhere in the body for use (e. ATP). Though not shown in this figure, insulin appears to indirectly act on malonyl- Co. A, a potent inhibitor of CPT I, one of the most important mitochondrial enzymes that facilitates the oxidation of fatty acids. High levels of insulin promote fat storage and inhibit fat oxidation, and low levels of insulin promote fat mobilization or release along with fat oxidation. If this sounds crazy – the notion that insulin plays such a crucial role in fat tissue — consider the following two clinical extremes: type 1 diabetes (T1. D) and insulinoma. In the former, the immune system destroys beta- cells (the pancreatic cells that make insulin) – this is an extreme case of low insulin. They literally lost all fat and muscle. I’ve tried to size the arrows accordingly to match their relative contributions of each input and output. The first figure, below, shows a state of fat balance, or zero net fat flux. Input #1: De novo lipogenesis, or “DNL” – Until the early 1. It was about 5%, hence the tiny red arrow under a state of fat balance (i. A very important point to be mindful of, however, is this: this represents an average throughout the body and does not differentiate specifically between, say, DNL in the liver and DNL in the periphery (i. This limitation is not trivial, but rather than focus on the very specific details of this paper, I’d rather use it as a framework for this discussion. The 1. 99. 5 paper also examined what happened to DNL during periods of over- and under- feeding CHO and fat.)(*) Marc is on the Scientific Advisory Board for Nu. SI, so perhaps I’m biased in my admiration of him and his work. Input #2: Re- esterification, or “RE” – In a state of fat balance, RE is largely composed of dietary fat sources that are not immediately used, but rather stored for later use. For the purpose of simplicity, this diagram does not show some portion of the L fraction returning to the RE fraction, though this is exactly what is happening in . Running is more than a good way to get in shape. Lace up and reap the many benefits of running today.A few years back, I wrote an article explaining 17 possible reasons why you’re not losing weight. It was a troubleshooting guide of sorts, aimed at helping people. This study, published in 1. Journal of Lipid Research, suggested that the RE process is a bit more complicated than simply re- assembling fatty acids on a glycerol backbone inside an adipocyte. For example, someone like me who is in fat balance (i. I’m neither gaining nor losing fat mass at this point), has virtually zero DNL, but quite high RE, especially after meals. Well, not so fast. This is where one actually gets the energy (ATP) from fatty acids. The same hormones and enzymes that promote L, directly or indirectly act on other intermediaries that promote oxidation, more or less. The converse is also largely true. Brief digression: I’m always troubled by folks who have never tried to take care of someone who is struggling to lose weight (fat), and who themselves have never been overweight, but who insist obesity is . This is probably the most rapid state of negative fat flux a human can experience. So what we do about it? I do not believe there is only one state, shy of total starvation, which will assuredly put you in state of negative fat flux. Yup, this is probably (though not necessarily) going to work, depending on how “profound” is defined. This is where the discussion gets really interesting. The rationale, of course, is provided by the first figure above (from the textbook) and a slew of clinical studies which I will not review here (see Gardner JAMA 2. Ludwig JAMA 2. 01. Shai NEJM 2. 00. 8 to name a few). But, the bigger question is why? Why do most (but not all, by the way) people with excess fat to spare who are on well- formulated carbohydrate- reduced diet lose fat? Or, do they eat less because they are losing weight? I suspect the later. They are not giving up fat from their fat cells because they are eating less. If you can’t wait, which I can understand, I highly encourage you to start scouring the literature for Mark’s work. What?, you say, doesn’t this violate the First Law of Thermodynamics? What differentiates those in this camp (I was in this camp) from those above (point #1), is unclear to me. I’m not stating the obvious – that the deliberate EE is higher – that is clearly true. I’m suggesting resting EE is for some reason more likely to rise in this setting. It is also possible that this increase in free/available energy results in an increase in deliberate EE (i. They could be partly or mostly responsible for this. The literature is quite dilute with respect to this question, but in my experience (feel free to dismiss), it is not uncommon to see a reduction in cortisol and an increase in testosterone (I experienced about 5. Today, however, I don’t consume this much, closer to 3,8. I have always found the term “metabolic advantage” to be misleading, though I’m guilty of using it periodically. The question is not, does it exist? The questions are, why does it only exist in some people, what relevance does it have to fat loss – is it cause or effect? In my experience (and Gardner’s A TO Z trial seems to validate this, at least in pre- menopausal women), about 2. RQ environment. Using the Ornish diet as the example from this paper, I suspect the reason is multifactorial. It restricts sugar, flour, and processed carbohydrates. So, I don’t really know how likely it is to lose weight on a eucaloric diet that is 6. CHO and 2. 0% fat, if the quality of the carbohydrates is very poor (e. It’s quite possible, of course, since ketosis results in a large L and implies a very small DNL. Fat flux is net positive. Still in ketosis, by the way (quantified loosely by fasting levels of B- OHB greater than about 0. M), but not losing fat. That’s the problem with multivariate algebra (and physiology). Many people who enter nutritional ketosis do so, I worry, because they believe it “guarantees” fat loss. I hope I have convinced you that this is not true. It comes with some advantages and some disadvantages, just like other eating strategies.
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