I’ve written before about the fact that many people in the area of obesity research have the opinion that obesity is simply the result of eating more calories than the body burns through metabolism and activity. My position, and that of a growing number of researchers, is that there’s more to obesity than calorie balance, and that body weight and fat mass is regulated by a complex system that involves an array of hormones and feedback mechanisms.
In recent months I’ve become interested in the potential role of a hormone by the name of leptin in obesity. I actually ‘got my brain round’ leptin by reader the blog of Dr Stephen Guyenet, who researches the ‘neurobiology of body fat regulation’. You can read his blog here.
Leptin’s main site of action appears to be the brain (hence the title of this post). Specifically, leptin acts on a part of the brain called the hypothalamus. It’s only the size of an almond, but the hypothalamus controls key bodily functions including hunger, thirst and sleep.
Leptin acts on the hypothalamus and does two main things:
• It speeds the metabolic rate
• It reduces hunger
Leptin sounds like a good thing to have around if we’re looking to maintain a healthy weight. Where can we get some? Leptin is actually secreted by fat cells (chemicals like leptin that originate in fat cells are termed ‘adipokines’). As we put on weight and fat, leptin levels generally rise. The action of leptin on the brain results in us eating less and gives a boost to our metabolism. These effects bring weight down again. As fats stores diminish, leptin levels come down and so we eat a bit more and burn a bit less.
Many researchers believe that leptin plays a key role in the regulation of the body’s weight and fat stores. Some have theorised that as long as leptin does its job properly, there’s no need to consciously control weight. Those individuals who eat what they like and maintain a steady weight probably have, among other things, a well-functioning leptin system.
But, and it is a big but, there is evidence that leptin doesn’t always do its job properly.
One reason for this can be inflammation in the hypothalamus. As a result, leptin doesn’t register so well here, and as a result the body is allowed to be ‘fatter’ than it would ordinarily be. Another reason why leptin may not do its job is because it can fail to get into the brain properly. The general circulation and brain as separated by a type of ‘filter’ known as the ‘blood-brain barrier’. Transport of leptin across the blood-brain barrier is inhibited by blood fats known as triglycerides. Triglycerides are formed in the liver and the major stimulus for their secretion is the consumption of carbohydrate. Eating carbs that cause spikes in blood sugar also stimulate inflammation.
Regular readers know that I am, generally, a fan of carbohydrate-controlled eating. Such diets can help to lower levels of insulin (the chief fat storage hormone) and tend to sate the appetite more effectively than diet low in fat and consciously restricted in calories. It seems another way these diets might help individuals lose weight is by allowing leptin to do its job.
Hi Dr. Briffa,
Thanks for the mention. Glad you found my posts useful. I added your blog to my blog roll, which I’ve been meaning to do for a while.
Can you comment on the fat set point theory as it relates to Leptin and other hormones? Specifically.. Do you believe the brain settles at a certain fat/obesity composition levels, or do you believe it is a continuum that is constantly responding to hormonal signals from the body? And how much do you believe obesity is regulated by interaction between hormones and cells in the body itself, vs the brain as a sort of central control point?
Hi Dr Briffa,
But don’t carbs trigger leptin release ? Therefore, lowcarb = low leptin ?
What are your thoughts on Irvingia gabonensis and it’s reported effects on leptin?
Ihave been on a reducing regime of prednisolone steroid for 4 years and have struggled with my weight. Could this medication have a n affect on leptin?
I concede I approach this from the point of view of a layperson.
Nonetheless, 26 months ago the work of certain authors directed me to the potential role of so called inflammation, or has Barry Sears has it, ‘slow inflammation’, has in the promotion of, perhaps, several ‘western’ conditions of ill health. Type 2 diabetes interested me in particular. Some of your own work, Dr Briffa, and of others, indicates that the causes of inflammation may well lie with dietary factors that might include consumption of too much carbohydrate* and consumption of the ‘wrong sort of fats or oils’. There may well be other dietary factors that could be promotional of inflammation, and other lifestyle factors also, but tested against a ‘litmus test’ of primal reasoning these two features do have the look prime suspects.
It is not uncommon for a GP to advise an overweight patient that being overweight puts them at greater risk of certain chronic diseases (though I note a study mentioned in the media this week questions the validity in this) and I came to sense intuitively that rather than simply being overweight being the cause of such conditions maybe the association would be that the causes of weight gain and the role of inflammation in being promotional of chronic conditions may have dietary factors in common.
Well, it can be hard to be certain in ones’ own mind, but the theme you put across that the function of leptin may be impaired and may lead to weight gain is interesting, and more so for the suggestion that leptin may be impaired by inflammation of the hypothalamus, in turn, via insulin, the result of dietary, and/or other factors.
If any of your readers, Dr Briffa, are new to these themes there was a BBC program, ‘The Big Fat Truth About Low Fat Food’, broadcast on BBC3 recently that set to question the merit of the lucrative ‘Low Fat’ food industry and its effects upon peoples weight and health. For those who think ‘low fat’ is the route to weight control nirvana it might be an eye-opener. It may be worth watching out for a repeat broadcast. Perhaps this fairly popularist program is an indication of a tide soon to turn? There’s a couple of days left to find it on iPlayer.
* or ‘too much’ of some property of common carbohydrate staple foods.
Thanks for this, and also for the great work you’re doing over on your blog.
I first learned about the fat set-point theory by reading Stephan’s blog. I’m open to it, as I am his view that it might be possible to re-set the set point. Re the ‘brain v body’ question, I believe that both have a part to play (this is pure speculation, by the way). I don’t really go with the reductionist view that obesity (or anything else) has one cause – I believe excess weight may be the result of many mechanisms that vary from person to person.
Have you got any data on this?
I have to confess I’d never even heard of Irvingia gabonensis but will have a look and may post on this.
Prednisolone is well known to have the capacity to cause weight gain, though the main mechanisms here probably have little or nothing to do with leptin directly.