The Fate of Fat

With each January 1st comes the ritual of the “New Year Resolution:” the commitment, more or less strong, to modify one’s behavior in the incipient year, typically positively, and oftentimes to better oneself. The practice is not new: people as far back as the ancient Babylonians had their own version of New Year Resolutions. These days, Americans regularly rank weight loss among their top objectives, which doesn’t seem too surprising if you consider the rates of overweight/obesity, and the socially-sanctioned, year-end national exercise-in-gluttony that starts around the fourth Thursday in November.

Photo: Wikipedia

When we consume too much food — in other words, when the food intake exceeds our metabolic energy needs — the unused carbohydrates and proteins are converted to triacylglycerol (dietary fats simply get lipolyzed/esterified). It seems likely that evolutionary pressures have favored these neutral fats as a major energy reservoir for two main reasons. (1) Fatty acids are more reduced than carbohydrates and proteins: complete oxidation from fatty acids yields about 9 kcal/g whereas that from carbohydrates and proteins yields about 4 kcal/g. (2) Another reason is that triacylglycerol (also called triglycerides) are anhydrous: the more polar carbohydrates and proteins are more highly hydrated than the less polar triglycerides. For instance, 1 g of glycogen (a polymer of glucose, a common and simple carbohydrate) binds about 2 g of water. As a consequence, 1 g of anhydrous fat stores about 6 times as much energy as 1 g of glycogen!

Fatty acids play several key roles in metabolism. Oleic, palmitic, and linoleic acids are the three most common fatty acids used for energy storage in adipocytes in the form of triglycerides. Photo: Wikipedia

For most people, losing weight actually means shedding that very efficient energy storage (or at least some portion of it), while preserving muscle mass. But where does that fat actually go? Australian scientists Andrew Brown and Ruben Meerman posed that question to a sample of physicians, dietitians, and personal trainers. To their dismay, most of these professionals answered that it was transformed into energy/heat. This would appear to violate the fundamental law of conservation of mass credited to 18th century French chemist Antoine Lavoisier.

The Aussie duo set out to find the answer for themselves. They wanted to account for each atom found in a typical triglyceride (with formula C₅₅H₁₀₄O₆) as it is oxidized into carbon dioxide (CO₂), water (H₂O), and energy, summarized in the following reaction (similar to that for the complete oxidation of glucose that perhaps more people are familiar with):

C₅₅H₁₀₄O₆ + 78 O₂ → 55 CO₂ + 52 H₂O + energy

We can fairly easily derive the amounts of O₂ required to completely oxidize 1 mole of this average triglyceride, as well as the amounts of CO₂ and of H₂O produced in the process. What the authors proposed to elucidate here was the proportion of the triglyceride that contributes to carbon dioxide and to water. In other words, if you have 10 kg of fat to oxidize, you know that you will need to inhale around 29 kg of O₂, and that you will produce roughly 28 kg of CO₂ and 11 kg of H₂O (roughly 11 L of water); but how much of that 10 kg-mass actually goes into the carbon dioxide, and how much into the water? Meerman and Brown delved into the literature, and came across experiments performed by Lifson and colleagues in the late 1940’s, tracing isotopic oxygen (O ¹⁸) to show that molecular oxygen becomes distributed in a 2:1 ratio between CO₂ and H₂O via the carbonic acid buffer reaction:

CO₂ + H₂O ⇌ H₂CO₃

In other words, CO₂ and H₂O will share the 6 oxygen atoms from the triglyceride that helped give rise to them in a 2:1 fashion, with 4 O atoms going to carbon dioxide, and 2 to water. Using the atomic mass (in dalton), we can now compute the percentage of mass of this average triglyceride that will be contributing to carbon dioxide formation, and the percentage that goes into water formation.

Of the average triglyceride C₅₅H₁₀₄O₆ (or 861 Da),
55 C (or 661 Da) + 4 O (or 64 Da) contribute to 55 CO₂: ((661+64)/861) x 100 = 84.2%
and
104 H (or 104Da) + 2 O (or 32Da) contribute to 52 H₂O: ((104+32)/861) x 100 = 15.8%

So about 84% of the triacylglycerol goes into carbon dioxide, and roughly 16% goes into water. This means that most of the fat mass is lost through exhaling carbon dioxide! Beyond this nifty calculation, what does this actually mean? It remains to be seen whether reinforcing these concepts in “secondary school science curriculums and university biochemistry courses,” as the authors advocate, will do much to help people shed unwanted weight. I posed this question to a friend of mine who knows a lot more about fat than I do, and he was not much impressed either: “Don't really see how this could aid in weight loss. Still comes down to how many calories you eat vs how many you expend,” said Yann Ravussin, PhD. Indeed. But at the very least, this should reaffirm to people, lay and professional, the centrality to weight loss of proper respiration during exercise.

References:

Berg, J., Tymoczko, J. L., Stryer, L. Biochemistry, Fifth Edition; 2001, pp 601-603.

Lifson N, Gordon GB, Visscher MB, Nier AO. The fate of utilized molecular oxygen and the source of the oxygen of respiratory carbon dioxide, studied with the aid of heavy oxygen. J Biol Chem 1949;180:803-11.

Meerman, R., and Brown, A. When somebody loses weight, where does the fat go? BMJ 2014;349:g7257