Bro Endocrinology


This is because the normal pattern of weight gain might not be to slowly accumulate very small amounts each day, but rather to be weight stable for protracted periods, interspersed with periods of gross imbalance during which most weight gain occurs. For example, weight gain during the holiday season in the United States (from Thanksgiving in November until the new year) is significantly higher than during the rest of the year (Yanovski et al., 2000) and is matched by seasonal variation in food intake (de Castro, 1991), although other studies have shown no change in overall weight but an increase in fatness over the same period (Hull et al., 2006). ...

The UK Department of Health, for example, recently convened an expert working group to quantify the magnitude of weight change and energy imbalance in the UK population, concluding that the average weight gain was 6.7 kg [14.8 lbs] over 10 years and that the daily energy imbalance necessary to generate this was about 25 kJ/day. The conclusion that is often drawn from these weight gain and energy balance calculations is that our bodies must therefore contain an exquisitely tuned system that controls our intake and expenditure with incredible precision to maintain our body mass at an almost constant level. From a treatment perspective, it is probably this tuning system that has made the pharmacotherapy of obesity such a challenge with regards to efficacy.



However, it is notable that obesity in most humans is not associated with mutations in the gene encoding leptin (Maffei et al., 1996; Speliotes et al., 2010).


Set point

The set point model is bolstered by the observation that, when the system is perturbed – for example by a period of dieting (Luke and Schoeller, 1992; Dulloo and Jacquet, 1998; Hainer et al., 2000) or overfeeding (Leibel et al., 1995; Bouchard et al., 1988; Bouchard et al., 1990) – people lose or gain weight, respectively. However, once dieting or overfeeding ceases, they tend to regain any lost fat, or lose the accumulated fat, and return to a level approximating their original fatness (Bouchard et al., 1996; Anderson et al., 2001). Moreover, they modulate energy expenditure to resist the perturbation in intake (Deriaz et al., 1992; Tremblay et al., 2004; Rosenbaum et al., 2010; Rosenbaum et al., 2008; Rosenbaum et al., 2003; Rosenbaum et al., 1997; Leibel and Hirsch, 1984). This means that the amount of weight loss or gain is less, and the speed at which weight returns to baseline levels is more rapid, than would be predicted by only a passive system that was regulated by unchanging mean intake and expenditure levels. Indeed, this set point model in which the body defends a level of adiposity is often used to explain the common phenomenon of weight regain following acute weight loss and the failure of dieting as a strategy to promote prolonged weight loss (Anderson et al., 2001).


Settling point

An analogy for the regulation of body energy stores as explained by the settling point model is the levels of water in a lake (Fig. 2). In any system in which there is a reservoir (such as body fat stores) with an input (food energy) and an output (energy expenditure), the reservoir of the system comes to a natural equilibrium if either the inputs are downregulated in proportion to the reservoir volume, or the outputs are upregulated in direct proportion to the reservoir volume.

In other words, imagine a lake surrounded by hills, and disregard evaporation and ground absorption. If it rains over the lake, the level of the lake will rise, but more of the body of water will be above its local ground level, causing more water to flow out. If there's a sufficiently prolonged drought, the water will lower until it's all below its local ground level and no more water can flow out.

In human terms: if you gain weight, your maintenance energy increases. This makes intuitive sense as a potential cause of the obesity crisis: if there's overeating but not undereating, some of that overeating will cause weight gain. But this alone can't explain diet rebounds; the body seems to 'remember' its earlier weight.

To understand how such a system might operate, it is useful to consider, for example, an individual who eats 12 MJ per day, expends 12 MJ per day and weighs 70 kg, and is in energy balance. Imagine that the person is placed on a 9 MJ per day diet, resulting in an intake flow to the reservoir that is lower than the output. The discrepancy between input and output of 3 MJ is expected to result in weight loss, comprising some fat and some lean tissue that is burned to supply the shortfall between intake and expenditure. Now, owing to the lack of this fat and lean tissue, which previously required metabolic expenditure, the person’s daily expenditure will be less than 12 MJ, and the discrepancy between intake and expenditure will diminish. This passive response occurs owing to the inevitable reduction in expenditure caused by decreasing fat and lean body mass. Any discrepancy between intake and expenditure will therefore tend to disappear over time because of changes in storage that diminish the discrepancy. Once fat and lean tissue have decreased to a point where expenditure is 9 MJ per day, the individual will be back in energy balance and no further weight loss will take place. This condition of re-established balance occurs because of the link between the reservoir (fatness) and the output (expenditure).

Maybe failure to adjust the diet for further weight loss? Return to pre-diet habits? We have intuitive senses of how much food to eat normally; could these persist? Cf. heroin addicts who get clean, relapse, and overdose, because they're used to accounting for a tolerance that they no longer have.

Imagine that the same individual then goes back to eating 12 MJ per day. The discrepancy between intake and expenditure is now in the opposite direction, which leads to an increase in body mass. This slowly causes an increase in expenditure, which will eventually return to 12 MJ per day, and there will no longer be an imbalance or weight gain. Crucially, however, the body will reach this balance when the body composition has returned to the same state it was in before the diet started. To an outside observer who is unaware of the actual control system, this return to the original body composition could be misinterpreted as the individual defending a level of adiposity.


Research anthropology

Hirsch pointed out that much of the obesity research field is effectively split into two groups – physiologists-molecular biologists-geneticists and behaviourists-psychologists-nutritionists – each functioning more or less independently of one another.