A Possible Explanation of Appetite, Obesity, Leptin Resistance, and Type 2 Diabetes and Insulin Resistance.
Copyright 2012, James Michael Howard, Fayetteville, Arkansas, U.S.A.
Very briefly, I suggest appetite and a connected disorder of appetite found in obesity, leptin resistance, may be explained by the ratio of testosterone to DHEA.
It is my hypothesis that testosterone evolved to increase absorption of DHEA by cells / tissues. I think DHEA was selected by evolution to increase gene activity. Increased absorption of DHEA was stimulated by increased androgen receptors produced by testosterone. For example, I think humans evolved because of increased maternal testosterone. The effect is increased androgen receptors by human brains in utero. Therefore, our brains, because of increased gene activity, are bigger. The increased use of DHEA by our brains produced bigger brains at the expense of body development. My point is that tissues / cells compete for available DHEA. Optimally, a ratio of testosterone to DHEA is established for proper growth and development and maintenance. (For more detail regarding the relationship of testosterone and DHEA: “DHEA, Estradiol, Testosterone, and the Relevance of Their Ratio …The Androgen Receptor …and the Secular Trend,” at: http://anthropogeny.com/Androgen%20Receptor%20and%20Secular%20Trend.htm ). (Humans produce more testosterone than any of the great apes and the amount of testosterone produced by the great apes directly parallels their relatedness to humans. See the chart at www.anthropogeny.com .)
Leptin reduces appetite. Leptin is higher in women than men. Does testosterone reduce leptin? Sugar and high energy foods decrease testosterone and leptin. DHEA is higher in men than women. I think it more likely that DHEA reduces leptin levels. It does this by increasing leptin receptors. I suggest that part of the gene activity induced by DHEA results in increased gene activity of various receptor molecules. Therefore, if testosterone increases DHEA which increases leptin receptors, among others, then measurable leptin will be lower in men than women. The ratio of higher testosterone in men increases absorption of DHEA which increases leptin receptors which decrease leptin levels. Now, back again to evolution, lower testosterone may increase appetite in women which would be conducive to fat deposition which would be advantageous to pregnancy.
Leptin resistance is characterized by high levels of leptin. That is, leptin is not being absorbed. I suggest this results from low levels of DHEA or low levels of DHEA in cells / tissues because of low testosterone. Leptin is produced mainly by “white” adipose tissue. It is known that DHEA reduces white fat production. Therefore, a normal cycle is produced; when sufficient fat is deposited, leptin is produced to reduce appetite. I suggest low DHEA allows increased production of white fat which increases leptin. However, the problem is that obese people produce abnormal levels of white fat and leptin without a reduction in appetite. Leptin increases without its normal effect. This is leptin resistance.
It is known that testosterone and DHEA are low in obesity. If testosterone is low, then DHEA does not readily enter cells. Low DHEA reduces gene activity which, among many things, reduces receptor production, including reduced leptin receptors. I suggest this results in increased leptin, increased fat production because of lack of appetite reduction, and a cycle which further increases fat and its production of leptin, or leptin resistance.
Since testosterone and DHEA both decrease with age, aging increases fat deposition and appetite. It is part of my work that the “secular trend” is caused by testosterone. (You can see my explanation on the lower, left side of www.anthropogeny.com .) Of consequence to this discussion, the secular trend may represent an earlier rise of testosterone followed by an earlier decline of testosterone within our population. This would result in an early reduction of testosterone and DHEA which would result in increased obesity and leptin resistance.
I suggest the common problem, “insulin resistance,” is caused by the exact mechanism just described above but involving insulin receptor production. This could, therefore, explain why type 2 diabetes is increasing directly parallel to obesity. Many, many researchers attribute the increase in type 2 diabetes to obesity because of this parallel increase. I suggest they are simply caused by the same thing, which is the alteration in the testosterone to DHEA ratio that is occurring at an increasingly higher percentage with time within our population.