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I've recently been reading about leptin and leptin resistance and I have a question that has been nagging me. It seems like one of the first things that researchers tried after the discovery of leptin was leptin injections in rats to see if it would suppress hunger. Instead, the rats get hungrier and that led people to believe that large amounts of leptin could lead to leptin resistance.

My question is, why do steroids (which increase testosterone) work while leptin injections do not work? From my understanding, steroid users cycle usage to avoid resistance; why can't the same be done with leptin injections?

NOTE: I don't use steroids or advocate for them. I'm simply wondering why increasing a given hormone seems to work in one situation, but not in another.

closed as off-topic by JohnP, user2861, Matt Chan Oct 18 '14 at 13:32

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    While this is a great question, it's not really on topic unless you can relate it to your own fitness program. How would knowing this information help your own fitness goals? As it stands, it's interesting trivia. – JohnP Oct 10 '14 at 14:55
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Hormones get over simplified sometimes. The broscience would go something like this: "If you want to get bigger, inject testosterone. If you want to get skinnier, inject leptin."

The reality is that your endocrine system is way more complicated than that, and leptin is a good example. This is an excerpt from Dr Richard Atkinson (endocrinologist):

[Leptin] is made by fat tissue, and as you get fatter, you make more of it. That was quite a shock because everybody thought that obese people were going to be deficient in leptin. With the more recent understanding of leptin resistance, it makes no sense to give people leptin if they have an impaired response. The resistance is still there. No amount of leptin is going to overcome that resistance.

Giving leptin only helps in a few extremely rare cases in the world in which people make no leptin at all, which causes them to overeat and become obese. When those people received leptin by injection, they stopped overeating and lost weight. But for the vast majority of people, the treatment won't work, nor is leptin approved as a medical treatment for weight loss.

In other words, the problem isn't a lack of leptin but rather an insensitivity to it (which is caused by obesity). So rather than looking to leptin to reverse obesity, obesity needs to be reversed so that leptin can function normally. From a 2007 study:

Lastly, we show that by decreasing the fat content of the mouse's diet, leptin responsiveness of NPY/AgRP and POMC neurons recovered simultaneously, with mice regaining normal leptin sensitivity and glycemic control.

Leptin does work, but you only need enough. And for folks who need it to lose weight, they have to lose weight for the leptin to work.

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