We’ve all heard that being overweight or obese is unhealthy. We know that being “fat” is undesirable in most of the world. Every day doctors tell their patients about the importance of losing weight to reduce their risk of heart disease and type II diabetes. But, how many of us actually know exactly why that extra fat is so bad for our health? How does obesity affect our risk of developing disease and what is the best way to restore our health? In this blog post, I begin these questions.
Two major problems associated with obesity are an overabundance of free fatty acids (FFAs) in the blood and inflammation. Today, I’ll explain the role of FFAs. In my next post, I will explain the role of inflammation.
A FFA is a small lipid that has been cleaved from a larger fatty acid molecule. In the body, FFAs generally serve as a fuel source. In healthy individuals, fatty acids are the predominate energy source used during periods of fasting (about 3 hours after the last meal). When a meal containing carbohydrates is consumed, the molecular machinery in the cell can quickly switch to using glucose as the main energy source. After the glucose is consumed, the body will again switch to mainly metabolizing fat1.
This metabolic flexibility is lost in obese individuals. Studies have shown that obese people burn more glucose and less fat in a fasting state than healthy people. After a consuming a carbohydrate-containing meal, obese people burn relatively less glucose and more fat than healthy people1.
Insulin resistance in obese individuals is a major cause of metabolic inflexibility. Insulin is the hormone that is released in response to an increase of glucose in the blood (after carbohydrate consumption). In healthy individuals, insulin causes cells to uptake glucose from the blood. This lowers blood glucose levels, which is important because high blood glucose can cause an array of serious health consequences, as seen in diabetic individuals.
Obese people are resistant to the effects of glucose. That is, their cells are less apt to take up glucose in response to insulin. As a result, blood sugar levels increase and more insulin must be produced and secreted by the pancreas.
So, why do obese individuals become insulin resistant? A major factor is that an of excess free fatty acids (FFAs) in the blood blunts the insulin signal2. Obese individuals have more FFAs circulating in their blood simply due to the fact that they have more fat in their bodies3. There is a sort of over-flow effect where the liver struggles to store the excess fat, thus the fat remains in circulation in the blood. The FFAs interfere with the insulin-signaling pathway and lead to a decreased sensitivity to the insulin signal.
Since the insulin signal is less effective, more insulin must be produced and secreted in order to lower blood sugar. This taxes the beta-cells in the pancreas, which produce insulin. Over time, the beta-cells become “worn out” and die, and type II diabetes occurs. This is why type II diabetes often occurs in obese people4.
In a fasted state, obese individuals rely more heavily on glucose metabolism and less on fat metabolism for energy than healthy individuals1. Additionally, more fatty acids are present in the bloodstream3. Thus, the turnover rate of fatty acids is reduced in obese individuals. This allows more time for these fatty acids to be damaged, and create particles like oxidized LDL. An excess of oxidized fats, like oxidized LDL, can increase risk of heart disease5.
When a person loses their metabolic flexibility, it is easy to get into a cycle of weight gain. In a fasted state, obese individuals have higher glucose metabolism and lower fat metabolism than they should. So, when the body burns most of the available glucose in the bloodstream, instead of burning fat, the body produces signals telling the brain that it needs more fuel. This can cause intense hunger, even though the body actually has plenty of fat stores. As a result, an obese person is likely to overeat and gain more weight.
In my next post, I’ll write about the health effects of inflammation as a result obesity and possible ways to overcome the issues associated with obesity.
1. Kelley DE. (2005). Skeletal muscle fat oxidation: timing and flexibility are everything. J Clin Inv 115(7): 1699-1702.
2. Roden M. (2003). How free fatty acids inhibit glucose utilization in human skeletal muscle. News Physiol Sci 19: 92-96.
3. Mittendorfer B, Magkos F, Fabbrini E, Selma Mohammad B, Klein S. (2009). Relationship between body fat mass and free fatty acid kinetics in men and women. Obesity 17(10): 1872-1877.
4. Kahn SE, Hull RL, Utzschneider KM. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature Rev 444: 840-845
5. Weinbrenner T, Schroder H, Escurriol V, Fito M, Elosua R, Vila J, Marrugat J, Covas M. (2006). Circulating oxidized LDL is associated with increased waist circumfrense independent of body mass index in men and women. Am J Clin Nutr 83: 30-35.