

Professor Robert Lustig explains that leptin resistance - and sugar - is at the root of the obesity epidemic


Waistband feeling a bit tighter, or buttons straining after Christmas?


In a fascinating new book, Robert Lustig, a professor of clinical paediatrics at the University of California, expounds a whole new scientific theory.

He argues that the urge to overeat and lounge around doing nothing is not a sign of weakness.

It is, he says, a hormonal issue, triggered by eating too much sugar.

He points the finger of blame at the hormone leptin, which acts like an appetite thermostat.

As one of two ‘hunger hormones’ in the body, leptin works to decrease the appetite (its partner, ghrelin, increases appetite).

When you have had enough to eat, your fat cells release leptin, which effectively dulls the appetite by instructing the brain that it’s time to stop eating.

But Professor Lustig warns that our sweet tooth is sending this process haywire.


For many years scientists thought obesity could be caused by a shortage of leptin — thinking that without adequate levels, overweight people simply never received the message that they were full.

But more recent studies have shown that obese people have plenty of leptin (in fact, the fatter you are, the more of it you appear to have), but are more likely to be ‘leptin-resistant’.

This means the cells in the brain that should register leptin no longer ‘read’ the signals saying the body is full, but instead assume it is starving — no matter how much food you continue to eat.

In panic, the brain pumps out instructions to increase energy storage — instigating powerful cravings for high-fat, high-sugar foods because these are the easiest and most immediate forms of energy — and conserve energy usage, by dampening any urge to get up off the sofa and go for a run.

The food cravings are made even more intense — and impossible to resist — because leptin is supposed to dampen the feeling of pleasure and enjoyment you get from food by suppressing the release of the brain chemical dopamine, helping to decrease appetite.

But if you are leptin-resistant, food never stops tasting delicious, no matter how much of it you eat.

This, says Professor Lustig, is why many overweight people find it so hard to stop eating, and why diets so often fail.


Scientists have been struggling to work out what causes leptin resistance.

But now Professor Lustig and his team have been able to show — in repeated studies on humans — that too much sugar in the diet is to blame.

High sugar diets lead to spikes in the hormone.

This is needed to clear sugar out of the blood and into storage as fat.

But repeated insulin spikes, due to a high sugar diet, can lead to a condition called ‘insulin resistance’ (when the cells have been so bombarded by insulin they no longer respond to it).

Professor Lustig believes insulin resistance triggers leptin resistance, and, crucially, he has discovered that by reducing insulin levels it is possible to improve ‘leptin signalling’ (the brain’s ability to read leptin), stop cravings, put the brakes on food consumption — and trigger weight loss.

In his new book Fat Chance, Professor Lustig explains that leptin resistance — and sugar — is at the root of the obesity epidemic.

A high sugar diet can trigger leptin resistance even if you are just slightly overweight. This is because sugar triggers a spike in insulin


He believes 1.5 billion overweight or obese people in the world suffer from this condition — and is convinced that the problem can be tackled by targeting insulin.

In his studies, many participants took insulin-lowering drugs, but the professor says similar results can be achieved by a few small lifestyle changes — notably reducing sugar in your diet.

The professor has a heavyweight background in endocrinology (the study of hormones), as both a medical doctor and academic.

He used organised trials to study  the role the brain plays in governing appetite and activity levels and found that patients who had damage to the hypothalamus (the area of the brain that controls energy levels) could not lose weight, but somehow gained weight even when restricted to a near-starving 500 calories a day.

Lustig realised that a similar process could be happening with obese adults and set out to investigate a potential solution.

His studies revealed that the roles of leptin and insulin are intertwined, and bind to cells in the same area of the brain — the hypothalamus.



While leptin activates biochemical reactions that send ‘satiety signals’ to the brain, insulin can very effectively block these signals, resulting in no satiety, no sense of fullness, and uncontrolled eating of high fat, high sugar foods.

This is leptin resistance, and leaves the brain ‘blind’ to leptin signals, so it still thinks we’re hungry.

Even worse, in healthy people, one of the things leptin should do is to tell the brain to reduce insulin production. It does this by dulling appetite and thus reducing food intake (so cutting the body’s need to produce yet more insulin to deal with the food).

But if you have too much insulin and you are leptin-resistant this doesn’t happen, and insulin levels rise ever higher, creating a vicious cycle.

Lustig believes that our high sugar diets cause continually stimulated insulin production.

He says the insidious creep of insulin resistance means that our bodies now produce double the insulin for every teaspoon of sugar consumed compared to 30 years ago.

He says insulin resistance is now so widespread, it affects the majority of overweight people and even as many as 40 per cent of those who are normal weight (if they eat too much sugar and refined carbohydrates like white flour, bread, pasta and rice).

And leptin resistance becomes more of a problem with increasing body size: ‘Plump people might have a little leptin resistance, but the morbidly obese will have a lot,’ he says.


Professor Lustig believes that our high sugar diets cause continually stimulated insulin production


The sweet, processed food that makes up so much of the modern diet (much of it disguised as ‘low fat’ and therefore healthy) has addictive qualities — particularly for those caught up with leptin resistance.

When we eat food, the brain chemical dopamine is released, creating a feeling of pleasure and reward, explains Professor Lustig.

Then leptin kicks in to suppress the release of dopamine, so that we get less reward, and therefore we stop eating.

But, he adds, if you’re leptin-resistant, the dopamine won’t be suppressed properly, and it remains at high levels in the brain, and ‘floods’ the brain cells.

After many meals (over a period of about three weeks) brain cells may start to become ‘tolerant’ to these persistently high levels of dopamine.

They build up resistance, meaning that higher and higher amounts of dopamine are needed to trigger a reward signal.

As a result, you may feel compelled to eat greater quantities to achieve the same sense of satisfaction. This can swiftly turn into sugar addiction.

Insulin also works to clear dopamine from the brain, gradually blunting the reward felt for further food.

But if you’re insulin-resistant too, the brakes won’t work, and the reward impetus continues unabated.

This, Professor Lustig believes, explains why many people can want, and apparently enjoy, never-ending quantities of food even when energy stores were long ago full — for example over the Christmas period.

He fears insulin resistance (and therefore leptin resistance) may also start in the womb, and that exposure to high sugar diets — via the mother — may trigger genetic changes that increase a baby’s risk of insulin and leptin resistance in later life.

But he adds: ‘At the end of the day, it is what you eat (and of course, how much of it) that puts the final nail in the coffin.’


Conventional wisdom and government policy still blame dietary fat for our ever-rising obesity levels (and horrific heart disease statistics).

However, Professor Lustig is part of the band of obesity specialists who question the validity of the hugely influential research conducted in the Fifties, which identified dietary fat as the trigger for weight gain and heart disease.

The seminal ‘Seven Countries’ study by U.S. epidemiologist Ancel Keys in the Eighties demonised fat, triggering a massive change in food manufacture.

In an effort to make low fat food more palatable, many manufacturers raised the carbohydrate level, adding quantities of sugar to almost everything (both sweet and savoury).

For instance, a small pot of low fat yoghurt can contain as much as four teaspoons of sugar, and even wholemeal bread hides two teaspoons per loaf.

Gradually tastes and eating habits have changed, Lustig says, resulting in growing populations worldwide inadvertently hooked on easy-to-eat high sugar foods.

As he puts it: ‘The obesity epidemic was born in the aftermath of this seemingly logical and well-meaning, yet tragically flawed understanding of our biochemistry.’

Mercifully, it is not all doom and gloom.

‘Obesity is a hormonal problem and hormones are alterable,’ says Professor Lustig.

He recommends simple steps, detailed below, that can lower your leptin levels.

These include reducing sugar in every recipe by a third, increasing your fibre intake, and taking just 15 minutes of activity every day.

Adapted from Fat Chance: The Bitter Truth About Sugar,  by Robert Lustig, published by HarperCollins on January 3 at £13.99.

© Robert Lustig 2013. To order a copy for £9.99 (postage and packing free), call 0844 472 4157.



Professor Lustig believes the key to losing weight is to reverse leptin resistance. Here is his action plan:

Have just one dessert a week

When cooking, reduce sugar in every recipe by a third, and eat dessert as a treat, once a week.

Fibre leads to weight loss

Fibre is now routinely stripped from foods to give a finer texture and extend shelf life (manufacturers have found food with fibre doesn’t freeze well, and can’t be cooked quickly), but according to Professor Lustig: ‘Fibre, or roughage, is the most misunderstood weapon in our nutritional arsenal.’

This is because the digestive system has to work to strip away the outside bran of a wholegrain, so slowing the whole digestive process, and stopping glucose levels from peaking suddenly.

This means less insulin is released, therefore less energy is stored as fat. Slower digestion also gives your brain a chance to register that you are full.

Take 15 minutes’ exercise daily

Exercise alone cannot cause significant weight loss (unless you change your diet at the same time) but Professor Lustig says 15 minutes a day is enough to improve your insulin sensitivity (because activity helps cells become more receptive to insulin), and build muscle at the expense of fat.

Although you may not see a drop on the scales, by improving insulin sensitivity and lowering insulin levels, exercise, will improve leptin signalling.

Eat like your Grandma

Beware packaged food. Professor Lustig’s mantra is: ‘Don’t eat anything your grandmother wouldn’t recognise. If the food has a company logo you’ve heard of, it’s processed.’

Don’t eat on your feet

Eating standing up means you will be eating fast, with no time for satiety signals to kick in, says Professor Lustig.

Always include some sort of protein (chicken, pulses) in every meal (to slow the digestive process and reduce the risk of insulin spikes) and avoid any ‘food’ that is just fat, carbohydrate and sugar (such as doughnuts, milk-shakes, pastries).

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