Obesity...inflammation...diabetes

I think we have touched on these ideas before, but the research in these areas continues. (I really need to get back to some postings about exercise or physical activity. All this stuff is too biochemical. I suppose I'll just have to wait until the exercise journals are published again.)

So we are back to obesity being an inflammatory condition which itself promotes insulin resistance. (There is a vicious circle here).

Anyway, this article reminds me of something Art Devany wrote:

While we are on the subject of inflammation it should be noted that obesity is a state of mild to less than mild inflammation. This is easy to see if you look at the redish faces of obese individuals. They also seem to have a look of pain or distress on their faces, which may truly be moderate pain from the inflammation. A theory I think may be right is 1. fat cells secret a variety of substances that promote inflammation (see the abstract below), and 2. local areas of fat tissue become hypoxic (short on oxygen) which induces oxydation of the fat and inflammation. Stringy, oxidized fat is linked to cellulite too if the supporting matrix becomes oxidized.

So on to the article from the Journal of Lipid Research......

Understanding how obese fat cells work

In obese individuals, fat cells are bloated and inflamed because they receive too many nutrients, including lipids. In these cells, various components cannot work properly anymore and, instead, they activate new proteins to cope with the situation. One of the most challenged organelles in obese fat cells is a maze-like compartment called the endoplasmic reticulum (ER) that makes proteins and lipid droplets and senses the amount of nutrients that enter the cell.

Margaret F. Gregor and Gokhan S. Hotamisligil review current knowledge about how the ER works in fat cells and is modified in obesity. They show that when a fat cell receives too many nutrients, the ER is overwhelmed and triggers a process called the unfolded protein response (UPR). This process is one of many cellular responses that activate proteins that increase inflammation and can even result in the death of the cell. UPR also causes insulin resistance, a condition in which the production and function of insulin – a hormone produced by the pancreas – is impaired and blood sugar is too high.

The scientists show that by better understanding how the ER works, it may be possible to devise a therapy that enhances the function of the ER and maybe improve the health of obese people. Already, two molecules that protect the ER from obesity-related stress have shown some success in mice. Called PBA and TUDCA, the molecules decreased blood sugar and insulin levels and improved overall response to insulin production.

ER stress may also be reduced by targeting molecules involved in the UPR process. For example, a drug called Salubrinal was recently shown to inhibit one of the UPR-involved molecules and to protect cells from ER stress-induced cell death. Also, there is emerging evidence that anti-diabetic drugs may also work, at least in part, through this mechanism.

A deeper knowledge of how fat cells become dysfunctional will be critical in devising successful therapies in the future, the scientists conclude.