Biology 202, Spring 2005
Second Web Papers
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In coming up with some reasons as to why an individual might be obese or even just overweight, a lack of will power or a large appetite are often mentioned. Using this as a starting point, if we know what area of the brain is responsible for controlling our appetite throughout the day we can discover a possible cause for obesity. In general, the hypothalamus is thought to be the control center for all homeostatic functioning, including hunger. It is currently believed that the hypothalamus achieves homeostasis by regulating bodily functions to adhere to various set points (3). For our current investigation, we will concern ourselves with the weight set point. What the concept of a weight set point means is that our hypothalamus will adjust for variations in our body weight above or bellow our set point by making us experience either hunger or satiation.

To discover how the hypothalamus is able to accomplish this, researchers preformed a series of brain lesions on different areas of a mouse's hypothalamus. From these experiments, they were able to deduce that the ventromedial hypothalamus is responsible for inhibiting an organism's experience of hunger (3). Damage to this area of the mouse's brain caused it eat whenever food was available regardless of how much it had already eaten. Conversely, when the lateral hypothalamus is damaged, the mouse would not eat and eventually starve itself to death no matter how much food was available (3). This made researchers believe that this portion of the brain was responsible for the hunger response. There are some flaws with this rather simplistic view of appetite and obesity. Firstly, how do we know that this pattern of anatomical responsibility is the same in humans as it is in mice? Teitelbaum provided more evidence against the dual center theory (stated above) in his experiment on a rat's motivation to eat (8). In this study, a normal rat's motivation to eat was compared to that of a rat with a lesion in the ventromedial hypothalamus by having them push on a lever to get food. At the beginning, when they only had to push the lever once or twice to receive food, the rats with the damaged brains show more of a motivation (were quicker to push the lever). But as the experiment progressed and they had to push the lever several more times in order to receive food, sometimes upwards of 200 times, the rats with the brain lesion showed significantly less motivation than the normal rats (8).

Besides there just being neuronal control over appetite exerted by the hypothalamus, there is also an endocrine control system that takes place largely at the same brain regions. In a series of studies conducted less than a decade ago, it was discovered that a relationship, similar to that between the ventromedial and lateral hypothalamus, exists between the hormone leptin and the neuropeptide NPY. Leptin is a hormone that is released by fat cells into the body's circulatory system (1). Once in our blood supply, leptin travels to the hypothalamus where it with two groups of receptor cells known as "anoretic" and "orexigenic". These cells are located in the ventromedial and lateral hypothalamus respectively. When leptin activates the "anoretic" cells, it causes them to release various appetite-suppressing neuropeptides (this is not surprising knowing the role of the ventromedial hypothalamus in appetite control). However, when leptin interacts with the "orexigenic" cells, it inhibits the release of NPY which regulates the hunger response in the lateral hypothalamus (1). It is believed that the ratio of leptin to NPY plays a large role in determining body weight. Normally, when fat levels are high they release a lot of leptin which helps decrease hunger levels. In obese individuals, although concentration of both leptin and NPY are relatively high, the receptors for leptin in the hypothalamus are desensitized, allowing the hunger reflex to go unregulated (4).

Another hormone which is thought to be very much involved with the onset of obesity and especially type II diabetes is insulin. Although it is not yet clear whether high insulin levels cause obesity or what the nature of the relationship between the two is, studies have been able to show that increased insulin levels in the blood can lead to an increased storage of fat in our bodies, hypertension, and atherosclerosis (5). Scientists have also been able to determine the function of insulin in our bodies. In response to an increase in blood glucose levels, the pancreas will release insulin into our circulatory system in order to aid in the absorption of glucose to the inside of the cell from the bloodstream (5). If insulin is not present in normal levels inside the body or if it is not able to function normally, as is the case with type II diabetes, glucose cannot be absorbed by our cells, leading to high blood-glucose levels (5).

Although scientists have had little success in identifying a "fat gene" responsible for weight gain in humans, it is still believed that much of the processes mentioned above have a genetic basis. For example, the rate of the genetic expression of several neuropeptides, such as NPY, is thought to have an effect on weight gain. However, there has been strong evidence supporting the idea that expression of certain genes can indirectly fight against obesity. An experiment preformed by Ron Evans and several members of the Salk Institute showed that the over expression of the PPARS gene in mice resulted in the conversion of fast oxidative muscle fibers to slow-oxidative muscle type (the type formed by regular aerobic exercise) (6). The results also showed that these mice burned more calories at rest than then normal mice, leading the researchers to believe that the expression of these gene helps fight against obesity (6). These finding lead us into a discussion of the social factors that play a role in obesity and its rapid increase to epidemic proportions in our population.

As mentioned in the analysis of the above experiment, the conversion to the slow-oxidative muscle type which helps fight against obesity can be achieved through regular exercise. This brings in a completely non-biological, will-based aspect to the cause and sharp rise in obesity rates: a lack of physical activity. This is what Frank Booth and Darrell Neufer point to as the cause of the obesity epidemic. In there article, they disprove the commonly held notion that the rise in obesity rates is the result a significant increase in our appetite and food consumption by pointing out that our caloric intake has actually decreased from hunter-gatherer times (7). Instead, they blame the cause of the epidemic on the increase of the ratio of caloric intake to expenditure from 3:1 in hunter-gatherer times to 8:1 in the present day (7). This means that we are using up a much smaller amount of the calories we take in daily through physical activity. And as for the cause of this decrease in activity? Booth and Neufer put the blame on such social influences as the Industrial Revolution and computer age (7). They contend that these "advances" in society have nearly eliminated the need for any physical activity in our daily chores such as transportation, agricultural practices, etc. Simply put, because we are doing less, we are gaining more

References

1. 1)How leptin may influence hypothalamus, appetite, and weight,

2. 2)Obesity and overwight,

3. 3)Appetite control system and brain, obesity,

4. 4)Obesity,

5. 5)Insulin, obesity and insulin-resistance syndrome,

6. 6) Evans, Ronald et al. (2004) Regulation of muscle fiber type and running endurance by PPARS. PLoS Biol 2(10):e294

7. 7) Booth- Frank, Neufer- Darrell. Exercise Controls Gene Expression

8. 8)PSY337: The neural control of feeding,


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