"me time"

have you ever suffered from pregnancy meltdowns (where you turn completely crazy for no apparent reason)? i had one last night....it was caused by the library calling to tell me to return "elmo's potty time" for the second time. i sat on the couch and shed some tears and said i need some "me time". it lasted about ten minutes...then i felt silly and ate ice cream.

ha....being pregnant- isn't it grand :)

*images courtesy of coco cozy, house of turquoise/atlanta home magazine, real simple (bottom two images)

The Body Fat Setpoint, Part III: Dietary Causes of Obesity

[2013 update: I've edited this post to remove elements that I feel were poorly supported.  I now think that changes in the setpoint are at least partially secondary to passive overconsumption of calories, particularly low quality calories]

What Caused the Setpoint to Change?

We have two criteria to narrow our search for the cause of modern fat gain:

1. It has to be new to the human environment
2. At some point, it has to cause leptin resistance or otherwise disturb the setpoint

Although I believe that exercise is part of a healthy lifestyle, and can help prevent fat gain and to some degree treat overweight, it probably can't explain the recent increase in fat mass in modern nations. This is because exercise doesn't appear to have declined. There are various other possible explanations, such as industrial pollutants, a lack of sleep and psychological stress, which may play a role. But I feel that diet is likely to be the primary cause. When you're drinking 20 oz Cokes, bisphenol-A contamination is the least of your worries.

In the last post, I described two mechanisms that may contribute to elevating the body fat set point by causing leptin resistance: inflammation in the hypothalamus, and impaired leptin transport into the brain due to elevated triglycerides. After more reading and discussing it with my mentor, I've decided that the triglyceride hypothesis is on shaky ground*. Nevertheless, it is consistent with certain observations:

• Fibrate drugs that lower triglycerides can lower fat mass in rodents and humans
• Low-carbohydrate diets are somewhat effective for fat loss and lower triglycerides
• Fructose can cause leptin resistance in rodents and it elevates triglycerides (1)
• Fish oil reduces triglycerides. Some but not all studies have shown that fish oil aids fat loss (2)

Inflammation in the hypothalamus, with accompanying resistance to leptin signaling, has been reported in a number of animal studies of diet-induced obesity. I feel it's likely to occur in humans as well, although the dietary causes are probably different for humans. The hypothalamus is the primary site where leptin acts to regulate fat mass (3). Importantly, preventing inflammation in the brain prevents leptin resistance and obesity in diet-induced obese mice (3.1). The hypothalamus is likely to be the most important site of action. Research is underway on this.

The Role of Digestive Health

What causes inflammation in the hypothalamus? One of the most interesting hypotheses is that increased intestinal permeability allows inflammatory substances to cross into the circulation from the gut, irritating a number of tissues including the hypothalamus.

Dr. Remy Burcelin and his group have spearheaded this research. They've shown that high-fat diets cause obesity in mice, and that they also increase the level of an inflammatory substance called lipopolysaccharide (LPS) in the blood. LPS is produced by gram-negative bacteria in the gut and is one of the main factors that activates the immune system during an infection. Antibiotics that kill gram-negative bacteria in the gut prevent the negative consequences of high-fat feeding in mice.

Burcelin's group showed that infusing LPS into mice on a low-fat chow diet causes them to become obese and insulin resistant just like high-fat fed mice (4). Furthermore, adding 10% of the soluble fiber oligofructose to the high-fat diet prevented the increase in intestinal permeability and also largely prevented the body fat gain and insulin resistance from high-fat feeding (5). Oligofructose is food for friendly gut bacteria and ends up being converted to butyrate and other short-chain fatty acids in the colon. This results in lower intestinal permeability to toxins such as LPS. This is particularly interesting because oligofructose supplements cause fat loss in humans (6).

A recent study showed that blood LPS levels are correlated with body fat, elevated cholesterol and triglycerides, and insulin resistance in humans (7). However, a separate study didn't come to the same conclusion (8). The discrepancy may be due to the fact that LPS isn't the only inflammatory substance to cross the gut lining-- other substances may also be involved. Anything in the blood that shouldn't be there is potentially inflammatory.

Overall, I think gut dysfunction could play a role in obesity and other modern metabolic problems.
Exiting the Niche

I believe that we have strayed too far from our species' ecological niche, and our health is suffering. One manifestation of that is body fat gain. Many factors probably contribute, but I believe that diet is the most important. A diet heavy in nutrient-poor refined carbohydrates and industrial omega-6 oils, high in gut irritating substances such as gluten and sugar, and a lack of direct sunlight, have caused us to lose the robust digestion and good micronutrient status that characterized our distant ancestors. I believe that one consequence has been the dysregulation of the system that maintains the fat mass "setpoint". This has resulted in an increase in body fat in 20th century affluent nations, and other cultures eating our industrial food products.

In the next post, I'll discuss my thoughts on how to reset the body fat setpoint.

* The ratio of leptin in the serum to leptin in the brain is diminished in obesity, but given that serum leptin is very high in the obese, the absolute level of leptin in the brain is typically not lower than a lean person. Leptin is transported into the brain by a transport mechanism that saturates when serum leptin is not that much higher than the normal level for a lean person. Therefore, the fact that the ratio of serum to brain leptin is higher in the obese does not necessarily reflect a defect in transport, but rather the fact that the mechanism that transports leptin is already at full capacity.

On image labelling

Labelling data is a labourous side task that arises in most computer vision projects. Since the developers usually don't want to spend their time for such a dumb work, there exist a number of workarounds. Let me enumerate some I've heard of:

1. At Academia, the task of labelling is usually being endured on [PhD] students' broad shoulders. The funny part is the students are not always enrolled in the relevant project. At Graphics & Media Lab, students who have not attended enough seminars by the time of revision, should label some data sets for the lab projects.
2. One could also hire some people to label her data. Since the developers/researchers are relatively high-paid, it is economic to hire other folks (sometimes, they are students as well). UPDATE: hr0nix mentioned in the comment that there exists the Mechanical Turk service that helps requesters to find contractors.
3. The more witty way is to use applied psychology. For example, Google transformed the labelling process to the game. During the gameplay, you and your randomly chosen partner tag images. Sooner you tag an image with the same tag, more points you get. The brilliant idea! Believe or not, when I first saw it, I was carried away and could not stop playing until my friends dragged me out for a pizza!
4. The most revolutionary approach was introduced by Densey Tan. Here is a popular explanation of what he has done. The idea is to capture labels straight from one's brain using EEG/fMRI/whatnot. Now they can perform only 2 or 3 class labelling, but (I hope) it is only the beginning.

The last point reminds me my old thoughts about the future of machine learning (or at least ML applied to Vision). Nowadays we deal with ensembles of weak classifiers, such as decision trees, stamps etc. One can use guinea pigs as weak classifiers! I suppose their brain is developed enough to understand 3d structure of the scene in the way human brain does, while modern computer vision systems lack for this ability. The animals are to be learned, for example, by experiencing an electric shock in case of wrong answers. Now, it is not obligatory to train "experts", it is sufficient to analyse their brain activity. Isn't it a breakthrough? :)

OpenCV bindings

If you are a computer vision researcher or an engineer, you cannot miss OpenCV library. Even if you are not, it could be useful to you. For example, here is a funny application: camera shots a programmer's face when a merge fails. If you are not familiar with the library, I recommend you to look through the list of its features on Wikipedia.

OpenCV is written in C to be extremely portable (for example, to DSP). The fact is C is not very popular nowadays. The recent release 2.0 contains (besides the other decent stuff) also C++ and Python wrappers. What about the other languages?

There are a number of C# wrappers. The most known is EmguCV, which is reported to be the only C# wrapper that supports OpenCV 2.0 (actually, I don't now what it means, but I suppose the API should correspond the C++ interface). It is distributed under GPL or the "Commercial License with a small fee".

As for Java, JavaCV seems to be the only viable wrapper. It also contains wrappers for other popular libraries like FFmpeg. It is also distributed under GPL, but the author promised to discuss weakening it if needed.

OpenCV was being supported by Intel, but it became a FOSS project recently. They are also going to participate in Google Summer of Code. If they will succeed, you might try to apply. I think it is a nice experience to develop such a popular library and be paid for it. :)

One of the fields they want to develop is augmented reality support for Android operating system. When I get known that there is an AR API in Android, I decided to try it. So, this is going to be a good opportunity!

UPD (Aug 6, 2011). There appeared a Haskell (!) wrapper for OpenCV by Noam Lewis.

Also, OpenCV folks are developing the official Java wrapper. Looking forward to use it!

just because

i really like these images....

i'm off to get my weekly shot. it's loads of fun but it's keeping my little man safe and sound and hopefully (fingers crossed) preventing me from going on bed rest.

*images courtesy of aubrey road/ martha stewart, everything fabulous