Estrogen, Leptin, and Obesity
Fair warning: the following is sexist in the way only evolutionary biology can be.
Females are, individually, more valuable than males. Until they hit menopause that is (at which point they become worthless). This is how our bodies work, don’t shoot the messenger. As manifestation and proof of this concept we can examine susceptibility to cardiovascular, cerebrovascular, and metabolic diseases. In order of least to greatest risk: pre-menopausal females -> males -> post-menopausal females. From the standpoint of passing on genes, it is important for females to be able to stay healthier for the span of time necessary to produce offspring, for as long as they are offspring production capable. After that point, the body stops caring. But don’t worry, scientists don’t.
Researchers like Deborah Clegg are working quite hard to understand what exactly happens at that crucial dividing line. The most obvious change? A stiff decrease in the amount of estrogen in the body. Okay, but how does that affect health? Glad you asked. I just had the pleasure to sit through a lecture given by Dr. Clegg, and it provided several fascinating insights:
1) Metabolic activity, hunger response, and eating behavior is largely controlled by a protein known as leptin. When you give excess leptin to pre-menopausal females it prompts a dramatic change in their eating behavior (and possibly metabolism) that leads to weight loss. No such similar response exists in males or post-menopausal females. Interestingly, we have known about the general effect of leptin for ages, although the male/female divide is new info (New info that makes it seem pretty silly that when drug trials were done on leptin to see if it could be used as a diet pill they used an all male test group. Missed opportunity that.)
2) This sex-specific/age-specific behavior is because estrogen is a necessary co-factor in leptins function. Estrogen both is necessary for the transport of leptin across the blood brain barrier and the activity of nuclear estrogen receptors increases production of leptin receptors. There are a number of ways to demonstrate how critical estrogen is to this, but perhaps the best is that if you give males or post-menopausal females estrogen injections, it allows for the response to leptin seen in pre-menopausal females.
3) Hormonal birth control can mimic some of the effects of menopause. By suppressing the normal ovulatory cycle and exchanging the peak of estrogen activity during ovulation for a regulated, lower estrogen level, the door is opened for the flood of nasties that most females shouldn’t have to worry about until after their child-bearing days are over. Indeed, Dr. Clegg’s data suggest that in the absence of prevalent hormonal birth control, there would be little to no obesity or obesity correlated illness among pre-menopausal females. Of course, my common sense suggests that there might be a little bit of a trade-off here, and that a few extra pounds could beat a baby in the cost/benefit analysis.
Afterthought (2/11/2011): Corrected some typos. It occurs to me that I should, for the sake of clarity, note that the above applies in mice/humans, it probably extends to other animals but probably not beyond mammals. Maybe not even beyond placental mammals.
Sources & Further Reading
- Once again this is based on the fascinating research of Deborah Clegg, whose recent publication list is available here
- Dr. Clegg will be appearing in a 2012 documentary on the obesity epidemic in America, although I was remiss in not catching the name.