Metabolic Damage, Energy Intake & the Human "Energy Thermostat" - An Update Based on Recent Studies

You may argue that it is unfair, but there's no way to negate that people who have been sign. overweight once are at a high risk of ending up with a reduced metabolic rate when they've achieved the same weight and body comp. as people who have never been obese.

You will probably have heard of, maybe even experienced the nasty reduction in basal energy expenditure that occurs during and often persists after energy restricted diets. In today's SuppVersity article, I will briefly summarize the results of a couple of recent studies that may yield new insights into a phenomenon some people call "metabolic damage".

Now, "metabolic damage", or as I prefer to call it, the diet-induced (semi-)permanent down-regulation of our basal energy expenditure wouldn't be a problem if our appetite would decrease to the same degree. Unfortunately, there's a disconnect between appetite and energy expenditure of which a recent study from the University of Leeds suggests that it may be particularly pronounced in the obese.

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As J.E. Blundell et al. point out, the prevailing model of homeostatic appetite control envisages two major inputs: (1) signals from adipose tissue and (2) signals from peptide hormones in the gastrointestinal tract. As a SuppVersity reader you are familiar with both inputs - the role of leptin and adiponectin and the satiety hormone induced appetite reduction.

Figure 1: An increase in energy expenditure increases the already existing correlation between total daily energy intake and the amount of fat-free mass in obese individuals (Blundell. 2015).

In contrast to the amount of lean mass which is a decently reliable predictor of energy intake in both lean and (especially active) obese individuals, neither the total amount of fat mass, nor the signals it's sending are reliable predictors of energy intake in the obese. The signalling system appears to be disturbed in both obese (too much leptin + leptin resistance) and reduced obese (too little leptin for the remaining body fat) individuals.

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What's the reason for "metabolic damage": In contrast to the acute effects of dieting on energy expenditure and the subsequent loss of the linear relationship between fat-free mass and energy expenditure, the potentially long-lasting reduction in energy expenditure in reduced obese individuals (obese men and women who lost enough weight to return to normal weight), is probably mediated by a lack of relative leptin expression. Their (now empty) fat cells trick the center that controls their energy intake into believing that there's much less body fat left than is actual-ly the case - that's at least the most promising hypothesis.

Only recently, Teresa Jiménez Jaime and colleagues from Universidad de Chile confirmed in a three-month study on twenty-two women aged 23-44 years with a body mass index (BMI) of 25-32 kg/m² who underwent a calorie restriction treatment (20 kcal / kg initial weight) and were encouraged to increase their physical activity.

Figure 2: Changes in resting and total energy expenditure during diet + exercise intervention (Jiminéz Jaime. 2015).

In the compliant group, the scientists observed a sign. reduction in resting energy expenditure (REE) in absolute terms and adjusted for fat free mass (-164 ± 168 kcal/day (10,6%) and -4,3 ± 4,6 kcal/kg FFM (10,5%)). Accordingly, the significant correlation between FFM and REE (r = 0, 56 p < 0,05), that existed at the beginning of the study was lost at the end of the intervention.

What decides whether you end up "metabolically damaged" after a diet? We cannot answer this question for sure, but the risk will increase significantly if you lose more than 10% of your original body weight - even if most of the weight you lose is body fat. Eventually, this could be related to the changes in the fill level of the fat cells I hinted at in the red box, but all that is - as of now - not fully experimentally proven. It is yet obvious that genetics will also play an important role - people who are heterogenous for the ADRB2 gene, for example, appear to suffer significantly more pronounced reductions in REE in response to dieting than others (see Figure at the bottom | Camps. 2015). Scientifically sound evidence that you could ameliorate the effect by "reverse dieting", i.e. increasing the energy intake slowly after dieting or dieting down more slowly does not exist.

This was not the case in the subjects who didn't adhere strictly to the energy reduced diets. If we take into account that neither of the two groups lost sign. amounts of fat-free mass it is obvious that the mismatch between the theoretically required energy (i.e. calculated based on fat-free mass) and the real energy intake during a diet is mediated by a reduced energy expenditure that could be mediated, at least partly, by a borderline sign. reduction in thyroid function (the reduction in T3 and free T3 Jiminéz Jaime et al. observed didn't reach stat. significance). To become "metabolic damage" this reduction would have to persist even when the subjects returned to an energy sufficient diet.

Figure 3: Quotient of measured (RMRm) & predicted / calculated (RMPp) resting metabolic rate in subjects after 8w on a protein-enriched formula diet  that provided 2.1 MJ/day according to the relative weight change (Camps. 2013).

If we take a look at the data from a study by Camps et al. (2013), it appears as if it would depend on the amount of weight that is lost, whether this will or won't happen. Only the subjects who lost more than 10% of their body weight on a protein-enriched formula diet  that provided 2.1 MJ/day (51.9 grams of protein, 50.2 grams of carbohydrates and 6.9 grams of lipids) actually suffered from "metabolic damage", i.e. a disconnect between the measured (RMRm) and the predicted / calculated (RMPp) resting metabolic rate. And what's worst: The effect may diminish over time, but it won't disappear even after 44 weeks of eating "normal" again.

As usual, genes will also play a major role when it comes to the inter-individual differences in post-diet "metabolic damage". While we are far from fully understanding this relationship we do already know that subjects with the AA allele of the ADRB2 gene appear to be more susceptible to a weight loss induced reduction in resting metabolic rate (Camps. 2015).

So what? As of now, there appears to be very little you can do about the larger than expected reduction in energy expenditure that occurs when obese individuals lose more than 10% of their body weight. In view of the fact that the Camps and Jaime studies show that the reduction in basal energy expenditure can be permanent and occurs irrespective of a loss of lean mass, it cannot be ascribed solely to either the temporary lack of dietary energy and respective reductions in energy expenditure or a diet-induced loss of metabolically active muscle or organ mass.

What remains as the most likely possible mechanism is a disturbed adipose tissue signalling of which I've argued in several previous articles and the red and blue boxes above that it is probably driven by the low lipid content of the increased number of hypertrophied fat cells, which mislead your body to believe that his fat stores were much lower than they actually are. Whether and to which extent a potential dysregulation of the satiety hormone cascade and first and foremost GLP-1 is involved as well and if and how the two effects interact still has to be investigated | Comment on FB!

References:

• Blundell, J. E., et al. "The Biology of Appetite Control: do Resting Metabolic Rate and Fat-Free Mass drive Energy Intake?." Physiology & behavior (2015).
• Bray, GeorgeA. "Effect of caloric restriction on energy expenditure in obese patients." The Lancet 294.7617 (1969): 397-398.
• Camps, Stefan GJA, Sanne PM Verhoef, and Klaas R. Westerterp. "Weight loss, weight maintenance, and adaptive thermogenesis." The American journal of clinical nutrition 97.5 (2013): 990-994.
• Camps, Stefan GJA, Sanne PM Verhoef, and Klaas R. Westerterp. "Weight loss–induced reduction in physical activity recovers during weight maintenance." The American journal of clinical nutrition 98.4 (2013): 917-923.
• Camps, S. G., et al. "Genetic predisposition and energy restriction induced adaptations in resting energy expenditure and physical activity." How humans economize (2015): 93.
• Camps, S. G. J. A. How humans economize: energy restriction and end energy expenditure. Diss. Maastricht University, 2015.
• Jimenez Jaime, T., et al. "Efecto De La Restricción Calórica Sobre El Gasto Energético En Mujeres Adultas Con Sobrepeso U Obesidad." Nutrición Hospitalaria 31.6 (2015): 2428-2436.