This study shed some light on the genetics of obesity and the role of gene expression in the etiology of obesity:
- Oliveira BAP, Pinhel MAS, Nicoletti CF, et al. UCP1 and UCP3 Expression Is Associated with Lipid and Carbohydrate Oxidation and Body Composition. PLoS One. 2016;11(3). doi:10.1371/journal.pone.0150811
Their final point is UCP3 expression was associated with BMI, percentage of lean body mass (%LBM), and %FM in the postoperative period even after adjustment for age (Table 3). This simple diagram also helps explain.
Studies have suggested that genetic factors contribute to the development of obesity. Indeed, approximately 40–70% of the variation in susceptibility to obesity can be attributed to genetics.
Recently, four novel and heterozygous mutations in the UCP3 gene were identified (V56M, A111V, V192I, and Q252X) (Musa et al., 2012). Children carrying these mutations exhibited a higher percentage of fat and BMI, which was associated with dyslipidemia and lower insulin sensitivity (Musa et al., 2012).
Another article gives more insight.
- Musa CV, Mancini A, Alfieri A, et al. Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage. Int J Obes (Lond). 2012;36(2):207-217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279655/. Accessed April 28, 2019 doi:10.1038/ijo.2011.81.
The fasting state probably reduces UCP1 expression even more, leading to even more efficiency (lower expression of UCP1). So, basically, with post-protein-sparing modified fast (PSMF) or weight-loss surgery, patients extract every possible value they can from the calories they eat due to down-regulation of UCP1. Down-regulation seems like the most obvious explanation for weight regain despite taking in the same amount of calories (the so-called “your body remembers its previous weight” comment is useless and oversimplified, since the body is not a memory circuit or a hard drive).
The article disagrees with that, and notes that they couldn’t identify a change in UCP1 expression. However, with an N of 13, it is pretty obvious in their diagram (see A for UCP1) that a larger study would likely find such a change in expression (or potentially, a small change is actually quite relevant). There is no way (yet) to induce UCP1 or UCP3 gene expression (though Vitamin D may help with UCP3 if it is low).
- Fan Y, Futawaka K, Koyama R, et al. Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles. J Biomed Sci. 2016;23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966724/. Accessed April 28, 2019 doi:10.1186/s12929-016-0271-2.
Uncoupling proteins (UCPs) are members of the protein family located in the inner membrane of mitochondria. These proteins participate in energy expenditure, thermogenesis, regulation of free fatty acids, and reduction of reactive oxygen species.
UCP1 plays an important role not only in thermal regulation but also in energy balance and weight control. A recent study conducted on experimental models of bariatric surgery detected the presence of increased body temperature and up-regulated brown adipose tissue UCP1 protein expression levels after surgical intervention. In addition to its action in the adipose tissue, UCP1 contributes to the ability of the organism to oxidize substrates, metabolize lipids, and reduce weight, so high UCP1 expression should prevent the development of obesity.
UCP3 is also involved in energy metabolism regulation and weight control. Recent evidence has suggested that UCP3 plays an important part in modulating the use of lipid and glucose as an energy substrate. Gaining a better understanding of the role UCPs play in controlling and maintaining energy substrate oxidation could help to manage obesity.
The best solution is increased muscle mass that increases the total energy expenditure. Which leads to pumping iron in order to build up the TOTAL UCP3 gene expression (since most UPC3 is in muscle) and, since the UCP3 iw low due to gene expression and gene variants. UCP1 is in adipose tissue, so there is probably no hope. The UCP1/3 discussion also explains why rapid weight cycling is so bad and so consistently seen/experienced. Since there is nothing you can do to alter UCP1, adipose tissue is very effective at storing calories.
That means ANY transgression (e.g., eating more than usual, eating worse, not exercising) will result in fairly rapid storage of the excess calories as fat. Thus, lifelong and consistent (on a daily basis) change is valuable. Unlike (or actually like) sleep, a patient can’t make up for a setback by simply doubling down the next period. Stopping cravings and other interventions are still key.
But, in the long-term, obese folks need to boost their energy expenditure if they ever want to eat more than a fasting diet. And the only/easiest solution I see is to boost UCP3 through more muscle vs. ever more continuous training (see rats on treadmills), which is going to get more efficient over time and require more and more exercise as muscles and cardiovascular functioning get more efficient. Or perhaps high intensity interval training (HIIT) would be better.
