Unravelling The Biology Of The Body Weight Set Point

sharma-obesity-balanceEvery dieter’s dilemma is the simple fact that our bodies can harness complex neurohormonal circuitry to counteract our volitional attempts at weight loss.

Short of starving yourself, there is a limit to the amount of weight you can lose (everyone eventually hits a weight loss plateau) and keeping it off is a lifelong battle as the body strives to return its weight back to the “setpoint” (usually the highest weight you’ve ever been).

But how exactly does this setpoint work and why can some people eat whatever they want – and even gain weight – without resetting to a higher weight?

We don’t know the mechanism in humans, but a study by Dirk Luchtman working in William Colmer’s lab here at the University of Alberta, published in PLOS provides intriguing insights into how this works in rats.

Their research used rats that were either sensitive or resistant to weight-gain induces by feeding them a high-energy diet (HED). Thus, they defined two groups of animals – those that fail to gain weight on HED (designated dietary resistant or DR) and those, who gain weight and then defend their higher body weight when put on a calorie-restricted diet (Defenders).

In their series of elegant experiments, the researchers were able to clearly show that even after prolonged exposure to a calorie-restricted diet, neurohormonal changes (such as the  GABA inputs to PVN neurons) in the Defenders maintained highly attenuated responses to hunger reducing signals (e.g. MTII) compared to diet resistant (DR) or normal weight rats.

This diminished response was only restored to “normal” after the Defenders regained the lost weight.

Thus, the authors note that,

“The loss of melanocortin sensitivity restricted to PVN of Defender animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint.”


Clearly, further understanding exactly why some animals (or people) find it easier to gain and maintain (defend) their higher weight is one of the key areas of interest in finding solutions to better prevent and treat obesity.

At least this much is clear – the reason why most rats (and people) fail at permanently losing excess weight is because of these complex neurohormonal mechanisms that will go to great lengths to ensure that you will eventually put the weight back on.

Simply put – this is exactly the biological mechanism that (if nothing else) argues in favour of considering obesity (once established) a chronic disease.

Berlin, Germany

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