Age-related Obesity


Many people successfully fight the "Battle of the Bulge" until they pass age 65 and then begin to loose the battle. Elevated mTOR turns the fight against you. The following from page 2 of Koschei, "Rapamycin prevents Obesity" explains:

1. mTOR decreases lipolysis (hydrolysis of triglycerides) (fatty acids); rapamycin increases lipolysis, releasing fatty acids from the fat tissues.

2. mTOR increases lipogenesis (synthesis of triglycerides; rapamycin blocks lipogenesis. 

3. mTOR promotes adipocyte differentiation and hypertrophy; rapamycin prevents adipocyte differentiation. 

4. Nutrients such as glucose, amino acids, and fats activate mTOR and increase insulin; rapamycin blocks mTOR and decreases insulin secretion and insulin-induced obesity. In a vicious cycle, obesity activates mTOR. 

5. Rapamycin prevents entry of lipoproteins into tissues. This can lead to elevated lipds. This is benign as rapamycin prevents atherosclerosis. However, the elevation of lipids can be blocked by using statins, part of the formula. 

In studies involving mice, rats and humans, rapamycin can decrease weight gain and prevent weight gain with rats on high fat diet. 

Rapamycin doesn't cause automatic weight loss in humans; but makes it much easier to lose weight on weight loss diet with reduced calories.

The decrease of central adipose tissue has very important metabolic impact because of hormone-like substances secreted by adipose tissue called adipokines. Central obesity is belly fat. Belly fat is bad, visceral adipose tissue is bad. However, adipose tissue on butt and extremities appears to be neutral. 

Most adipokines are harmful and increase with central and visceral obesity. Their most common effect is promoting chronic inflammation, which promotes atherosclerosis. 

Adiponectin, another very important adipokine, has beneficial effects; but the level goes down with increase of adipose tissue.

Creating a better adipokine pattern, as well as reduction of mTOR signaling is main goal of reduction of central obesity.