Food and Behaviour Research

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Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics

Lustig, R.H. (2006) Nature Clinical Practice Endocrinology & Metabolism 2 447-458 

Web URL: View this and related abstracts via Pubmed here. Free full text of this article is available online.


Childhood obesity has become epidemic over the past 30 years. The First Law of Thermodynamics is routinely interpreted to imply that weight gain is secondary to increased caloric intake and/or decreased energy expenditure, two behaviors that have been documented during this interval; nonetheless, lifestyle interventions are notoriously ineffective at promoting weight loss.

Obesity is characterized by hyperinsulinemia. Although hyperinsulinemia is usually thought to be secondary to obesity, it can instead be primary, due to autonomic dysfunction.

Obesity is also a state of leptin resistance, in which defective leptin signal transduction promotes excess energy intake, to maintain normal energy expenditure. Insulin and leptin share a common central signaling pathway, and it seems that insulin functions as an endogenous leptin antagonist.

Suppressing insulin ameliorates leptin resistance, with ensuing reduction of caloric intake, increased spontaneous activity, and improved quality of life. Hyperinsulinemia also interferes with dopamine clearance in the ventral tegmental area and nucleus accumbens, promoting increased food reward.

Accordingly, the First Law of Thermodynamics can be reinterpreted, such that the behaviors of increased caloric intake and decreased energy expenditure are secondary to obligate weight gain. This weight gain is driven by the hyperinsulinemic state, through three mechanisms: energy partitioning into adipose tissue; interference with leptin signal transduction; and interference with extinction of the hedonic response to food.


This important paper reviews the mechanisms underlying blood sugar regulation and appetite, showing how a high-sugar, low-fibre diet can lead to excessive production of insulin (which over time will promote insulin resistance, leading to poor blood sugar control and Type 2 diabetes), and explaining how this in turn can reduce the body's sensitivity to other hormones including leptin and ghrelin, which have powerful effects on appetite.

The result is that high-sugar foods and diets will lead to disturbances of both appetite and energy expenditure, which then help to create a vicious spiral of further overeating and weight gain.

Overweight individuals have always been told to 'Eat less and exercise more'. But as this paper makes clear, unless they also change the *kinds* of foods that they eat, this will be much easier said than done, because the high-sugar foods and drinks they crave can actually create fundamental disturbances in their own biochemistry and metabolism. 

If this analysis is correct, then consuming sugar to excess will effectively make people both greedier and lazier, via its effects on insulin and other hormones, which affect energy metabolism, appetite and behaviour. 

This in turn can help to explain why the standard advice for anyone tryng to lose weight - i.e. to reduce calorie intake, and expend more energy by increasing exercise - appears in practice to be so ineffective, if not counterproductive. 

See also the BBC News article on this research: