If you lose weight, you better make sure your leptin is functioning properly

This time of year will generally see a lot of people embarking on changes designed to shed some excess weight. The problem is that although many people will lose weight successfully, almost as many will regain that weight. Why? Well, a big part of the answer appears to be that when we lose weight, the body brings into play a range of mechanisms which help the body preserve its weight. One of these is a general dampening of the metabolism. Here’s how the authors of a paper published yesterday on-line in the American Journal of Clinical Nutrition describe it:

After weight loss, there is a decline in energy expenditure that reflects both the loss of metabolically active tissue plus an additional 300–400 kcal/d, which may be termed “adaptive thermogenesis…

In other words, metabolism reduces to an extent greater than is expected solely as a result of weight loss. For example, while body weight declines by 10 per cent, say, metabolism may fall by 15 per cent or more.

The authors go on to add:

Decreased energy expenditure after weight loss would have little consequence if it were easy to sustain a corresponding reduction in energy intake to maintain a reduced body weight. As anyone who has attempted to sustain weight loss can attest, this is not the case.

Well said.

Some of the mechanisms here included reduced activity in a part of the nervous system called the ‘sympathetic’ nervous system, as well as changes in hormones that affect metabolism including thyroxine and leptin.

Leptin is a particularly interesting hormone in that it secreted by fat cells and acts on a part of the brain called the hypothalamus to speed the metabolism and suppress appetite. I first became aware of the importance of this hormone by reading the blog of Stephan Guyenet. I ended up writing a blog post about it here.

As we gain weight and accumulate fat, more leptin is made (in theory) to help keep things in check. When we lose weight, leptin levels generally fall which can stifle the metabolism. It can also make people hungrier. One of the ways this can manifest is as reduced satisfaction from food. In other words, for a given amount and type of food people tend to feel less satisfied once they’ve lost weight than they were when they were heavier. The risk here, of course, is that people may then be ‘driven’ to eat more.

The paper published yesterday featured an experiment designed to assess the effects of leptin on people who had lost weight [1]. 10 obese individuals were fed a liquid diet offering 800 calories a day until they had lost about 10 per cent of their weight. This took anything from 36 to 62 days. Metabolism was measured before and after weight loss. Also, individuals were tested in terms of their response to eating including how satisfied they felt after food.

After weight loss, on separate occasions, individuals were injected with leptin or placebo (5 weeks each).
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  1. Total calorie burn fell by about 700 calories a day due to weight loss when individuals were injected with placebo. But with leptin, the reduction was much less (about 400 calories a day).
  2. Calories metabolism per kg of ‘lean mass’ (muscle) also fell as a result of weight loss, but this was not the case when leptin was being administered.

In short, leptin helped individuals maintain their metabolism after weight loss – just as we’d expect. Plus, when the individuals were on leptin, they derived more satisfaction for a given amount of food.

What we have here is some evidence, at least, that we stand a better chance of losing weight and keeping it off if we have good functioning leptin. Problems with leptin functioning – also known as ‘leptin resistance’ – is now emerging as a major factor in weight control issues. Inflammation in the hypothalamus appears to be one cause of leptin resistance. And one thing we can do here to help is to avoid foods that are inflammatory in nature. Spikes in blood sugar promote inflammation, so this is yet another reason for not eating a diet based on blood sugar disruptive carbohydrate including many starchy staples.


1. Kissileff HR, et al. Leptin reverses declines in satiation in weight-reduced obese humans. Am J Clin Nutr [epub 11 Jan 2012]

7 Responses to If you lose weight, you better make sure your leptin is functioning properly

  1. George Super Boot Camps 12 January 2012 at 7:25 pm #

    Aye, leptin is a pretty important hormone, although it’s only a part of the biochemical story.

    Lyle McDonald has a great series about Leptin here: http://www.bodyrecomposition.com/fat-loss/the-hormones-of-bodyweight-regulation-leptin-part-1.html

    And Martin Berkhan of Intermittent Fasting fame has a suspicion that I.F. partially inhibits leptin down regulation through being able to ingest large meals and decent calories instead of making each meal smaller.

    I’m sure there’s much more to come in this line of research and look forward to reading more about it from you.

    Keep up the good work,
    George Super BootCamps

  2. SamK 13 January 2012 at 5:20 am #

    Dr Briffa, An excellent resource for Leptin information is Dr Jack Kruse at http://www.jackkruse.com

  3. JT1 14 January 2012 at 2:34 am #

    Jack Kruse +1 – he can get very in depth but stick with him, his information is gold-dust.

  4. SJ 18 January 2012 at 12:07 am #

    I’m confused – the amount of weight lost is given as a percentage, but the reduction in metabolic rate is given as an absolute number. How much weight, on average, did these people lose? And what were their original maintenance calorie levels? A drop of 700 kcal/d seems enormous for only a 10% weight loss.

  5. Kevin eakins 22 January 2012 at 7:59 pm #

    I beileve that leptin resistance is primarly due to factors: toixicity in and around the hypothalamus (which causes the inlfammation) and overexposure to leptin itself as the amount of abdominal fat grows. Simply injecting more leptin is a poor therapy since all it will do is induce more leptin resistance making the bounce back even stronger when the injections are discontinued.


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