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Whenever one talks about the need to keep optimal weight in order to reduce cardiovascular risk and other health hazards, one will always quote the mantra – eat healthy and stay fit, which means keeping the desired balance between caloric intake and energy expenditure. The standard equation says that 7000 kcal equal 1 kg of fat, so, if the energy balance over a period of time points is (-)7000 kcal, this negative figure should also be expressed while standing on the scale, which should show 1 kg reduction in weight. All guidelines and recommendations are based on this formulation, and the scenario of failure to maintain or reduce weight despite keeping the instructions is attributed solely to poor adherence to the intervention program. Now it seems that there may be other explanations. A study published recently in [i]Science[/i] examined mice that were put in a system that could accurately measure both their caloric intake and energy expenditure [1]. Two groups were compared: normal mice and those with deletion of melanocortin 2 receptor accessory protein 2 (MRAP2), which are known to develop severe obesity at a young age. Even when fed the same amount of chow, null mice gained more weight than did wild-type mice. Only when the amount of food intake in null mice was further restricted to 10% (females) and 13% (males) less than that of wild-type mice was there equivalent weight gain. This was the case while mice were young but, at later stages of their life, the null mice demonstrated overt hyperphagia and associated weight gain.


  • Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel
    Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel


  1. Asai M, Ramachandrappa S, Joachim M, et al. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 2013;341:275-8.
  2. Novoselova TV, Jackson D, Campbell DC, Clark AJ, Chan LF. Melanocortin receptor accessory proteins in adrenal gland physiology and beyond. J Endocrinol 2013;217:R1-11.
  3. Chen AS, Marsh DJ, Trumbauer ME, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 2000;26:97102.
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