Bodyweight Regulation: Leptin Part 2

In the Bodyweight Regulation: Leptin Part 1, I talked primarily about leptin (and a bit about insulin,and a very little bit about the other hormones) and its discovery and how it may be the (or at least one of the) long-sought after hormones involved in regulating bodyweight. Today I want to take a quick look at what leptin is and how it’s regulated. Next time I’ll look at what leptin is doing (or not doing as the case may be).

Leptin is a protein hormone released primarily from fat cells although skeletal muscle, the gut and possibly the brain releases it too. But, in terms of overall quantity, fat cells are the primary place where leptin is synthesized and released.

Note: those of you still laboring under the false idea that fat cells are simply inert storage cells need to get out of the 1970’s and get up to date. Fat cells are turning out to be an endocrine organ in their own right, releasing a host of hormones and chemicals that have effects all over the body; leptin is but one of them.

Quite in fact, leptin scales scarily well with body fat percentage, as I noted on Wednesday, primarily with subcutaneous body fat percentage. The higher the level of body fat, the higher the leptin level and vice versa. Males below 10% body fat may have no detectable leptin in their bloodstream.

I’d note that, probably for hormonal reasons, women generally have 2-3 times as much leptin as men at any given level of bodyfat. There is also some evidence for gender differences in how leptin responds in women versus men to things like diet and exercise; more importantly, women’s brains may respond to leptin differently than men.

Tangentially, I suspect that this may be part of what’s involved in terms of why women generally have a harder time losing fat (a topic I discussed in some detail in my Bromocriptine booklet and that I’m delving even more heavily into right now).

However, leptin doesn’t only scale with body fat percentage, it is also related heavily to food intake, specifically carbohydrate metabolism in the fat cell.

In response to both over- and under-feeding, leptin changes quite rapidly.

When someone starts a diet, leptin may drop by 30-50% within about a week, obviously they haven’t lost that much of their body fat. After that rapid initial drop, drops in leptin are much slower scaling with body fat loss.

By the same token, with even short-term overfeeding, leptin can come up far more quickly than body fat is gained. This latter fact is part of the basic premise behind refeeding and cyclical dieting; short-term very high carbohydrate/caloric intakes can raise leptin without causing significant fat gain.

I’d note that, in the short-term, only carbohydrate intake affects leptin leptin levels; fat overfeeding has no effect. In addition, changes in fat mass per se don’t regulate leptin in the short-term (less than 48 hours). Rather, it’s the effect of glucose metabolism within the fat cell that is affecting leptin synthesis and release.

This is why my diets always base refeeds around periods of high-carbohydrate intakes, acutely this is the only way to affect leptin levels in the short-term.

In essence, leptin is telling your body two different things:

1. How much fat you’re carrying.

2. How much you’re eating.

From the standpoint of bodyweight regulation and physiology, these are important things for the body to know about.

I want to note again that, as I mentioned in the last post, insulin is also a player in bodyweight regulation, scaling primarily with visceral fat and there is evidence that men’s and women’s brains are relatively more or less sensitive to the two hormones.

Women’s brains appear to respond more to changes in leptin while men’s respond more to insulin. As you’d expect, these effects are probably mediated by differences in hormone levels and it appears that estrogen improves the sensitivity of the brain to leptin. While not tested in humans, estrogen injected into male rats increases the response to leptin.

As I discussed in a previous research review, there is also evidence that estrogen exerts a leptin like signal in the brain as well.

I’d mention that, from a practical standpoint (regarding refeeds), this doesn’t particularly matter in that both leptin and insulin will primarily be increased via high-carbohydrate refeeds.

In any case, leptin (and insulin and, of course, the other hormones I mentioned last time) are sending a signal to the brain about body fat levels and food intake, making them likely candidates for bodyweight regulation. So how are they working exactly?

That’s what I’ll talk about next time (still focusing on leptin but starting to address some of the other hormones as well).

Read Bodyweight Regulation Part 3



6 thoughts on “Bodyweight Regulation: Leptin Part 2

  1. I’m a female who has lost 160 lbs. I maintain a weight of 120 (within ~5 lb) and have for a few years (BMI ~20). I had long suspected I was severely leptin deficient as a result of weight loss. I confirmed my suspicions 7 months ago, when I agreed to participate in a study which replaces leptin in women who have leptin deficiency (because of my leptin deficiency I had been amenorrhetic for 4 years, and the study is about amenorrhea).

    Since replacing the leptin I feel so much better (mood, hunger, too many to list), and have resumed regular menstrual cycles. I feel like a normal weight person, before I felt starving (even when not acutely hungry, I always felt like a “starving person” ).

    I have long suspected women find it more difficult than men to lose weight primarily because leptin is a female hormone. Leptin is important in both genders, of course, but I think it affects women *way* more than men. A lot of women seem to be able to relate to my struggles after weight loss (mood, hunger, fertility). Men seem to respond to weight loss as if not much changed.

    I also definitely agree estrogen has “leptin like” effects; I’ve observed that I feel the most “leptin-like” when estrogen is highest (e.g. before ovulation). Doing research I discovered estrogen actually makes leptin, and estrogen controls how sensitive the brain is to leptin (injecting mice brains with leptin does very little if they are estrogen deficient; estrogen controls CNS response to leptin). Since leptin itself is necessary for adequate estrogen, we can see a feedback and direct relationship of leptin and estrogen.

    I disagree refeeds do much to really ameliorate leptin deficiency. Prior to leptin replacement, I did notice a day after a buffet pig out I felt “normal” and very good… but it only lasted a day, \which is far too little to counterbalance the amount of calories it took to create that feeling. I suspect that the leptin increase to overfeeding is proportional to the calorie excess created, and once a calorie deficit is recreated (either due to the satiety of the leptin or purposeful restriction) then the leptin will plummet again. This is my experience with refeeds, anyway.

  2. “Women’s brains appear to respond more to changes in leptin while men’s respond more to insulin. As you’d expect, these effects are probably mediated by differences in hormone levels and it appears that estrogen improves the sensitivity of the brain to leptin. While not tested in humans, estrogen injected into male rats increases the response to leptin.”

    This is extremely interesting since insulin causes less testosterone to bind to SHBG. Since men’s brain’s respond more to insulin it seems as if testosterone and estrogen (obviously the hormones that have the greatest difference in males and females) may be related to weight loss in males in females via insulin and leptin repectively.

    All in all, really interesting shit.

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