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Life Metabolism 2022年第1期1卷 10-24页

作者： John R.Speakman joel k.elmquist Shenzhen key Laboratory of Metabolic Health Center for Energy Metabolism and ReproductionShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina School of Biological Sciences University of AberdeenAberdeenUK State key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental biologyChinese Academy of SciencesBeijingChina CAS Center of Excellence in Animal Evolution and Genetics KunmingChina Departments of Internal Medicine and Pharmacology Center for Hypothalamic ResearchUniversity of Texas SouthwesternDallasTXUSA

People completely lacking body fat(lipodystrophy/lipoatrophy)and those with severe obesity both show profound metabolic and other health *** levels of body fat somewhere between these limits would,therefore,appear to be *** different models might be *** traditional is a set point(SP)where the levels are regulated around a fixed ***,dual-intervention point(DIP)is a system that tolerates fairly wide variation but is activated when critically high or low levels are *** DIP system seems to fit our experience much better than an SP,and models suggest that it is more likely to have evolved.A DIP system may have evolved because of two contrasting selection *** the lower end,we may have been selected to avoid low levels of fat as a buffer against starvation,to avoid disease-induced anorexia,and to support *** the upper end,we may have been selected to avoid excess storage because of the elevated risks of *** upper limit of control seems to have malfunctioned because some of us deposit large fat stores,with important negative health *** has evolution not protected us against this problem?One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary *** chance,it fell apart more in some people than others,and these people are now unable to effectively manage their weight in the face of the modern food *** understand the evolutionary context of obesity,it is important to separate the adaptive reason for storing some fat(*** lower intervention point),from the nonadaptive reason for storing lots of fat(a broken upper intervention point).The DIP model has several consequences,showing how we understand the obesity problem and what happens when we attempt to treat it.

关键词： obesity BMI body fat adiposity evolution selection adaptive leptin resistance metabolic programming dual-intervention point model set-point model

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