Revealed: Lipids are Sexist, Temporemental and Local Friday, Jul 1 2016 


 

When Baker et al. quietly published a gender-based difference in the concentration of lyso-phosphatidic acid (lyso-PA) in 2001 [1], it wasn’t taken all that seriously. This was partly because the methods they used for both isolating the lipid fraction and for profiling it were not conventional, and partly because it was quite a narrow result in the grander scheme of things. However, recent work by Sales et al. [2] might just be enough to broaden this observation. Sales et al. found that not only is there probably about a 10% natural variation in the lipid profile in healthy individuals, but that the profile of both lipids and fats is related to gender, the use of hormonal contraceptives and personal disposition.

Sales et al. report that there is a statistically significant difference in the blood plasma concentration of several lipids. This includes similar lyso-lipids to the lyso-PA targeted in the Baker study, but also larger fraction, mainstream lipids such as PC, PE, PI and sphingomyelin (SM) in healthy men and women in their 20s.

The differences between healthy women taking hormonal contraceptives and those who do not also appear to be significant, and they are also significantly different to the men. At first sight, the variation within each group is wider than the variation between groups, but student t-tests indicate that the likelihood of the difference in absolute values being down to chance is less than 5%, indicating a significant difference.

There is also evidence that the concentration of certain glycerides, including fats, is partly gender- and hormonal-contraceptive-dependent, with members of the latter group having higher triglyceride concentration than women who do not take hormonal contraceptives. This may have implications for treating illnesses related to lipoproteins, though further work is required to determine whether gender or hormonal contraceptives have a significant role in this.

This work is interesting enough on its own, but it comes shortly after another study, by Aviram et al., that showed that lipid distribution in certain parts of cells varies during the day [3] and a third, by Dawaliby et al. that showed that a lipid called PE is an important regulator of membrane fluidity in eukaryotic cells [4]. These studies between them show that the concentration of major structural lipids such as PE and PC vary throughout the day and are dependent on your gender and the pills you take.

These studies are juicy for lipid researchers because they support notions that lipid geeks like me have worked with for some time. For example, that the lipids we require for our cells to function are a dynamic and responsive group of molecules that we have yet to fully understand.

This work also raises a variety of questions. Are other factors important, like diet, temperature, the seasons etc.? What about the difference between the healthy systems studied and metabolic diseases? The list goes on. It also hints that lipids are under-rated parts of our cells that might be able to give away more information than we think.

References

1. D. L. Baker, D. M. Desiderio, D. D. Miller, B. Tolley and G. J. Tigyi, Analytical Biochemistry, 2001, 292, 287-295. 10.1006/abio.2001.5063.
2. S. Sales, J. Graessler, S. Ciucci, R. Al-Atrib, T. Vihervaara, K. Schuhmann, D. Kauhanen, M. Sysi-Aho, S. R. Bornstein, M. Bickle, C. V. Cannistraci, K. Ekroos and A. Shevchenko, Scientific Reports, 2016, 6, 27710. 10.1038/srep27710.
3. R. Aviram, G. Manella, N. Kopelman, A. Neufeld-Cohen, Z. Zwighaft, M. Elimelech, Y. Adamovich, M. Golik, C. Wang, X. Han and G. Asher, Molecular Cell, 2016, 62, 636-648. 10.1016/j.molcel.2016.04.002.
4. R. Dawaliby, C. Trubbia, C. Delporte, C. Noyon, J.-M. Ruysschaert, P. Van Antwerpen and C. Govaerts, Journal of Biological Chemistry, 2016, 291, 3658-3667. 10.1074/jbc.M115.706523.

 Banting Thin Friday, May 1 2015 


The broadest definition of lipids includes fats and cholesterol as well as biological amphiphiles. This means that the study of obesity is often regarded as part of the study of lipids. In fact, the study of obesity is a good broad definition of the clinical discipline of lipidology. The principal stuff of obesity is of course fat, referred to formally as triglycerides.

The structure of triglycerides give very little of their peripheral importance away: the social, emotional and even political meaning these molecules have is not at all evident from the molecules as we see them on the page. In fact, despite considerable research into human metabolism over the last hundred or more years, there has been very little impact on obesity. If anything, Europeans and North Americans are fatter now than they were a century and a half ago. This is despite the increase in our understanding of fats and the dangers they pose. This ‘obesity crisis’, if a crisis can happen as slowly as someone over-eating, also correlates with the popularisation of dieting.

In 1862, the undertaker by Royal appointment to the House of Hannover, a William Banting, published a ‘Letter on Corpulence: Addressed to the Public’. The document is still widely available, and makes interesting reading for social historians as well as lipidologists, and probably those interested in the psychology surrounding losing or gaining weight. It is about what became known as Banting, a form of dieting.

A look beyond the Victorian verbosity and veneration brings out familiar themes. He describes the perceived difficulties of corpulence—of being unfit, of having an awkward bodily shape, of lacking energy. He also fashions a superficially believable excuse for not increasing his calorific expenditure (taking more exercise), and hints at many of the ignorances of the time, including that fatness is age-related and that gout and obesity are linked.

Two particular things about this Letter stood out for me. First, that this appears to be an example of the belief that weight loss can, or should, or should only be attempted purely through dietary change. Second, that this is the first low carbohydrate diet, and forms the basis for all those that have been constructed in that vain since.

The idea that losing weight can be achieved through changes to diet alone is not necessarily wrong—no one who understood anything about human metabolism would tell you that it were—but equally there is no doubt that it is not the full story. The mass of triglycerides (amount of fat) in our adipose tissue can regarded rather like the amount of money in a bank account. If we spend more (take more exercise), the balance falls (we get thinner). If we earn more than we spend (eat more calories that are used), the balance goes up (our adipose tissue stores more fat). So, rather like running a current account, the balance between what is spent and what is earned is the key to changing the size of fat reserves. It is not just about what is earned.

Banting’s unwitting begattation of the ‘low carbohydrate diet’ is a bit harder to analyse. Certainly, he consumes fewer calories from starchy foods on his weight loss diet, to a level that he eats fewer than he needs and thus uses up his reserves. However, the diet also represents a considerable reduction in the intake of fat, and not necessarily as low a carbohydrate intake as one might imagine. He avoided pastry and fattier meats but also drank far more alcohol than is recommended today. The emergence of ‘low carb’ diets from this one is therefore a bit of a mystery. It was probably not widely understood in the 1860s was that fat contains more than twice as many calories as either protein or carbohydrate, gramme-for-gramme. Could it be that this is still poorly understood today?

Food is a complicated mixture of molecular species, and indeed the composition of foods is too complicated even to be at the centre of food science. Biochemical studies mean we now know that our omnivorous digestive systems and evolved metabolic machinery are well able to deal with a variety of molecular species. This means that we can tolerate a great variety in our diet. Our bodies can make fats out of both carbohydrate and protein, but cannot make either protein or carbohydrate out of fats. We can convert some protein monomers (amino acids) into others, and thus make up for a certain deficiency of amino acids in our diet, but by no means all—there are at least eight amino acids we must have in our dietary intake, the best sources of which are meats.

Human bodies are not really able to make carbohydrates at all–at least not ones for storing energy. Though we can get energy from fats, we rely upon carbohydrate absolutely. In fact, the basis of all terrestrial metabolism is the oxidation of glucose to carbon dioxide. Thus any organism that respites requires a supply of glucose. This means that although there is scope for a good deal of variety, the evidence is clear: there are some things we cannot expect to change.

However, the fact remains: no matter how clear the data, how good the science, or how thoroughly the fad diets and the bullshit of phrases like ‘low carbs’ are debunked, obesity remains. The science is not enough on its own, to stop the crisis. This suggests to me that the study of obesity is the study of the problem, more than the solution. Where the solution will come from is harder to say—but a hundred and fifty years of Banting has not yet given the answer.

References and Further Reading

Letter on Corpulence: Addressed to the Public, William Banting. (A simple google search will bring this up though links here, here and here work at the time of writing)

The Fats of Life, Caroline M. Pond. A dry and now somewhat dated but easy read on fats. More recent research includes evidence that illuminates our understanding of the genes involved in the metabolism of fats, see here.