Tara Parker-Pope, in the health blog section of the New York Times website, addressed in her post “A Diva’s Lessons on Weight and Beauty” the scientifically based concept that controlling body weight is not a matter of will power. Thank G-d, it’s finally dawning on the New York Times’ editors that fat people actually don’t deserve to be punished for their lack of will power (particularly after that awful Times magazine cover touting Clive Thompson’s misguided article (“Are Your Friends Making You Fat?”) on Christakis and Fowler’s research).

What many people don’t understand about the very important concept that controlling body weight is not a matter of will power is that people can still be healthy, or improve their health dramatically, no matter what they weigh. Everyone can make changes in their lives that will improve their health. It is absolutely true that a sedentary lifestyle combined with poor eating habits is clearly linked with disease, such as diabetes and heart disease. The important thing is the process of learning to incorporate healthier habits, while doing away with prejudice or discrimination against fat people. Shaming fat people will not lead to improvement in anyone’s health. Instead, it will continue to engender low self-esteem, unhealthy dieting practices that will slow down metabolic rates, and eating disorders. In short, the focus should be on learning to live a healthier lifestyle that doesn’t involve beating oneself up on a regular basis, based on one’s appearance or a number on a scale. Check out Linda Bacon’s website and the website for the Association for Size Diversity and Health.

After acquiring the book almost a year ago, I (again) started reading Gary Taubes’ book entitled Good Calories, Bad Calories. Based on what I’ve read so far, and knowing Gary Taubes’ background, I believe it’s a very scholarly work, and very thoroughly researched. From the title, it’s obvious that this book considers the scientific evidence for specific types of diets and how they affect body weight regulation.

In the first part of the book, in order to draw parallels with current scientific evidence for the “epidemics of obesity and diabetes,” Taubes puts forth a detailed historical analysis of the decades-long debate on whether dietary fat intake was the definitive cause of, rather than merely correlated with, the rapid rise in the incidence of cardiovascular disease in the developed world that started in the 1920s (when consumption of red meat increased considerably). The upshot of this work is to point out what happens when a researcher, who becomes prominent for various reasons, influences health care policy even when his/her scientific data are far from conclusive. In this particular case, Taubes discusses the work of the prominent physiologist Ancel Keys, who was convinced based on his research that the observed rise in incidence of heart disease was due to increased blood cholesterol levels, which was in turn due to increased total dietary fat intake. Keys was apparently a formidable character who felt very strongly that his data conclusively proved this hypothesis, and was very quick to strongly criticize those who opposed his theories. Throughout this time period, and even into the 1960s, there were many prominent researchers who had serious reservations about Keys’ theories, based on scientific analysis of his data as well as their own. Nevertheless, because Keys was so forceful, Taubes brings various elements to show that the media picked up Keys’ theories, and physicians who were faced with an alarming medical mystery began to recommend low fat diets to their patients, despite serious controversy over Keys’ data.

In such a scenario, the question becomes one of correlation versus causation, i.e., depending on how solid the scientific evidence is for any given observed public health phenomenon, one might be able to say there is a CORRELATION of an observed public health trend with disease, rather than being able to state, through a solid base of scientific evidence, that the observed trend CAUSES the disease. There is considerable scientific evidence demonstrating that the physical attribute of fatness does not conclusively indicate bad health, and that many  “obese” individuals are metabolically healthy.

One reason for this phenomenon of correlation overpowering the media is that it provides a solid message to address what appears to be an alarming trend. Often, people don’t have the patience to wait for conclusive scientific evidence to be produced when faced with a potentially scary scenario. When scientific evidence that contradicts the popular theory is published, it tends to be ignored, because it contradicts what has become DOGMA. This is what has happened with “obesity” research. Taubes skillfully points out that when scientifically observed correlations are not thoroughly researched scientifically, and they become socially accepted as dogma,  real scientific progress breaks down.

Part of the purpose of this blog is not only to examine the science behind metabolic regulation of body weight, but also to understand how current standards of beauty (read: thinness as opposed to fatness) evolved in modern Western culture. These two seemingly unrelated topics are actually very intimately tied together, as the ever-present, pervasive, all-encompassing, in-our-face images of our society’s ideals of beauty are so powerful that they have a profound effect on our perception of health. This is true for all members of our society, including health professionals.

This past Sunday my husband and I visited the Neuberger Museum of Art at SUNY Purchase. In their permanent collection of Modern Art were some examples of Dada Art. The Dada movement was started by a handful of artists, both American and European, who were deeply affected by the atrocities of World War I. The disintegration of societal norms during the war brought out in the Dada-ists a sort of nihilism and a desire to mock contemporary culture. The presence of the war in Europe drove many artists who were living in Paris to the relative peacefulness of the United States, where the Dada movement blossomed in the 1920s. There they found plenty of fodder for their cynicism in the industrial revolution and the rise of new forms of advertising. After viewing several Dada Art exhibits over the years, I finally realized I was on common ground with them.

At the Neuberger Museum, the piece that caught my eye and imagination was a gelatin silver print by Man Ray of Marcel Duchamp in a female alter ego whom they called Rose Selavy, which in French means “Eros, that’s life!” The original perfume ad was for “Belle Helaine, Eau de Violette”. In Man Ray and Marcel Duchamp’s version of this ad, the face of the woman, displayed prominently on the label of the perfume bottle, was replaced with the face of Rose Selavy, and the text on the bottle was replaced with the words “Belle Haleine, Eau de Voilette” which means “Beautiful Breath, Veil Water”. At first glance, this makes no sense, which is characteristic of Dada art. The description of this photo at the museum described its meaning best:

“This gesture (changing the image and text on the perfume bottle) alludes to the idea that (the reigning image of) feminine beauty (in the 20^th century industrial revolution) is not natural, but rather a social construction – a masquerade perpetuated in the images of women circulated in commercial and mass cultural forms like advertising and the cinema”. (text in parens is mine)

To Man Ray and Marcel Duchamp, feminine beauty lay much more in the spirit of the soul, rather than crass, glossy, manufactured images. Too bad their images and ideas were completely eclipsed by the power and money of advertising – this to the true detriment of our health as a society.

A “SNP” is a single nucleotide polymorphism. Within a genetically distinct population, i.e. people of a certain ethnicity, religion, or geographic region, there are several versions of the DNA sequence of any given gene that is almost identical, with the exception of one sequence unit at a specific site. This single nucleotide variation occurs in the population at observable frequencies. The Human Genome Project, a multinational collaboration to sequence the entire human genome (the DNA sequence in all 23 human chromosomes), opened the door to the discovery of many of these SNPs, which were present in genes thought to be very important in disease risk. The differences created by a SNP in a gene could give rise to a protein that could either increase or decrease the risk of getting a disease. Establishing the correlation of the frequency of occurrence of a SNP with the risk of getting a specific disease could lead to improvements in the health of an individual at risk, either by recommending specific therapies or changes in lifestyle or diet.

In a ground-breaking study entitled “Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colon Cancer Risk” (JAMA. 2008 Oct 1;300(13):1523-31), Virginia G. Kaklamani et al found a statistically significant correlation of a SNP in the ADIPOQ gene with incidence of colon cancer in a large cohort of subjects with Ashkenazi Jewish ancestry. This work is ground-breaking because it is the first published study to establish a real statistical correlation of a SNP based variant of the adiponectin gene with the incidence of colon cancer, after many circumstantial, indirect observations. Ironically, the SNP in the ADIPOQ gene was negatively correlated with colon cancer risk. In other words, individuals with the SNP containing GG or GC (found in 48% of all study participants) at the variant site were 27% less likely to develop colon cancer than those with the more common CC genotype. It is very important to remember, however, that as the authors caution, these results must be confirmed with further studies.

Adiponectin is an adipokine, or a hormone secreted by adipose tissue, that facilitates insulin sensitivity. Paradoxically, as adipose tissue mass increases, adiponectin levels decrease, and this is correlated with insulin resistance. Insulin resistance is correlated with elevated levels of other proteins, such as C-peptide and insulin-like growth factor binding protein-1 (IGFBP1) that is linked to increased risk of colon cancer. The results of this study suggest that there may be some identifiable genetic and biochemical connections between obesity, diabetes, and colon cancer.

Humans, mice — indeed all mammals — have two types of fat cells in their bodies; white and brown. White fat cells store energy. In contrast, brown fat cells dissipate energy as heat, thus counteracting obesity. Much to the chagrin of humans living in industrialized societies, most fat cells in our (adult) bodies are white fat cells. While this trait served our kind well throughout our evolutionary history, we now face a vast abundance of inexpensive, easily accessible, high energy content foods. This, combined with our body’s tendency to want to store up energy for times when food is scarce, leads to obesity and its accompanying adverse health effects. Wouldn’t it be great if we could have more brown fat cells and less white fat cells?

Scientists like Harvard Medical School’s Bruce Spiegelman would like to figure out a way to help us do just that! Spiegelman, who studies mammalian embryonic fat cell development, is conducting research to understand the adipogenic (i.e. how adipose, or fat cells arise) lineage. One key question that Dr. Spiegelman and his group seek to address is how white and brown fat cell fates are determined.

To answer this question, Dr. Spiegelman’s group performed a screen for molecular regulators including transcription factors that may be unique to either brown or white fat cells. The researchers identified a transcriptional co-regulator called PRDM16, which is expressed exclusively in brown fat cells. When the investigators studied the effect of increasing PRDM16 expression in white fat cell precursors in culture, they observed that the overall gene expression profile was distinctly that of brown fat cells. Then, they made transgenic mice that selectively overexpressed PRDM16 in white fat cells, and found that pockets of brown fat cells grew in the white fat cell depots. Similar results are obtained when mice are exposed to low temperatures for extended periods of time, or by prolonged exposure to b-adrenergic stimulation. Together, these results suggest that PRDM16 is an excellent candidate for a master molecular switch that can convert white fat cells into brown fat cells. However, since “suggestion” is not proof, the researchers performed additional experiments to investigate this.

To their surprise, the scientists found that when PRDM16 expression is inhibited in primary brown fat cells in culture, they differentiated not into white fat cells, but into myotubes, or skeletal muscle cells! This result suggested that brown and white fat cells did not come from one common progenitor cell type. Instead, they may in fact be two entirely separate lineages. Additional experiments provided strong evidence for this.

So where do these results leave Bruce Spiegelman and his group? The data showing that white fat cells can become brown fat cells by overexpression of PRDM16 still hold promise for therapy. Spiegelman aspires to make this type of therapy a reality, by employing a transplant model. White fat cells, which are easily obtained by liposuction, can be engineered to express PRDM16, and transplanted back into the original fat cell donor. These experiments are currently being performed in mice.

Important questions remain. For example, how many cells would be needed for the procedure to succeed, and how the body would respond to the engineered cells? Could these engineered “brown” fat cells lead to positive results by reducing obesity and restoring energy balance, or could there be negative effects? Bruce Spiegelman as well as many people suffering from obesity are sincerely hoping for the former.

This entry is based on a talk given by Dr. Spiegelman on Thursday, May 15, 2008 at the New York Academy of Sciences. Dr. Spiegelman was a featured speaker at the NYAS Conference on Integrative Physiology. I originally posted this entry on another of my blogs, Parallelaphors (http://parallelaphors.wordpress.com/), on July 30, 2008.