Fight Aging!

A large weight of evidence shows that excess body fat - and specifically excess visceral fat - is bad for you in the long term. Put on weight and your life expectancy drops, even as your lifetime medical costs rise. You will most likely be less healthy for the rest of your life than your leaner peers, and they will outlive you. (Unless of course medical technology advances rapidly enough to save you from the consequences of your diet and lifestyle choices. But that's no certainty; why gamble when you don't have to?)

Some fraction of the consequences of being overweight are actually the consequences of a lack of regular exercise. After all, there is a strong correlation between gaining fat tissue and not exercising, and causal links between the two work both ways. Stop exercising without altering diet, and you'll gain fat tissue. On the flip side of the coin, gain enough fat tissue and exercising becomes much more of a challenge.

Another fraction of the consequences of being overweight stem from the low-level reactions of your metabolism to the overnutrition required to create that excess body fat - the reverse of dietary restriction, but something that is not as well researched at the level of cells and genes, despite the vast real-life population study in overfeeding taking place in much of the world these days. You might note research on harms caused by a dietary excess of methionine, however, methionine being one of the triggers for calorie restriction benefits when dietary intake is reduced. It swings the other way too.

The real monster when it comes to fat tissue and long term health appears to be inflammation, however. Temporary inflammation is a necessary portion of the response to damage and disease by the immune system, but chronic, unremitting inflammation accelerates progress towards frailty and ill-health. Indeed, it shows up as a contributing factor in degenerative aging later in life as the immune system becomes increasingly damaged and erratic. This process is known as inflammaging in some parts of the research community.

Distinct from the aging of the immune system, fat tissue itself spurs chronic inflammation. This has been known for some time, and researchers have been chasing down a detailed explanation as to why this is so. You might look at the connection to macrophage behavior, for example, or cytokine signaling. The more visceral fat you have, the higher your level of chronic inflammation - and thus the more damage gets added per unit time to the state of your biology. Aging itself is nothing more than damage and the reactions of bodily systems to that damage.

Here researchers present a fairly detailed account of how they think fat cells are causing this issue. You might look at the original paper as well as the more digestible research publicity materials linked below:

Obesity makes fat cells act like they're infected

High calorie diets cause [fat] cells to make major histocompatibility complex II, a group of proteins usually expressed to help the immune system fight off viruses and bacteria. In overweight mice and humans the fat cells, or adipocytes, are issuing false distress signals - they are not under attack by pathogens. But this still sends local immune cells into a tizzy, and that causes inflammation.

"We did not know fat cells could instigate the inflammatory response. That's because for a very long time we thought these cells did little else besides store and release energy. But what we have learned is that adipocytes don't just rely on local resident immune cells for protection - they play a very active role in their own defense. And that's not always a good thing."

Could the inflammation caused by a high fat diet serve any purpose, or is it a senseless response to an unnaturally caloric diet?

"The expression of MHCII in adipocytes does not seem to be helpful to the body. It is not at all clear what the advantage would be, given all the negative long-term consequences of fat tissue inflammation in people who are obese, including insulin resistance and, eventually, full diabetes. This just appears to be a runaway immune response to a modern high calorie diet. The bottom line is, you're feeding and feeding these fat cells and they're turning around and biting you back. They're doing the thing they're supposed to do - storing energy - but reacting negatively to too much of it."

[If researchers] can identify the antigen(s) that MHCII is presenting to T cells in fat tissue, medical researchers would have a new approach to target adipose inflammation in obese patients. The hypothesis is that if a treatment can interfere with the production or MHCII presentation of these antigens, this would reduce the activation of fat tissue immune cells and thus reduce inflammation.