Joffe B, Zimmet P
Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Endocrine. 1998 Oct;9(2):139-41. doi: 10.1385/ENDO:9:2:139.
The basic premise of the thrifty gene hypothesis is that certain populations may have genes that determine increased fat storage, which in times of famine represent a survival advantage, but in a modern environment result in obesity and type 2 diabetes. The concept finds support in a unique animal model (Psammomys obesus) as well as among high type 2 diabetes susceptibility populations, such as North American Indians and South Pacific islanders. However, in some developing communities (e.g., Black South Africans) the thrifty phenotype hypothesis of perinatal malnutrition causing beta-cell dysfunction seems a better explanation, but this remains a contentious issue. Several genes have already been identified as candidates for the thrifty genotype, including those encoding proteins of the insulin-signaling and leptin pathways, as well as intermediary fat metabolism. Particular interest lies in the peroxisome-proliferator activated receptors. An innovative approach might be to focus on the "mirror image" of the thrifty genotype-congenital lipoatrophic diabetes mellitus, whose molecular defect remains enigmatic. We conclude that the genetic basis of the thrifty genotype probably derives from the multiplicative effects of polymorphisms at several sites mentioned above, rather than a single regulatory abnormality.
节俭基因假说的基本前提是，某些人群可能拥有决定脂肪储存增加的基因，在饥荒时期这代表着生存优势，但在现代环境中则会导致肥胖和2型糖尿病。这一概念在一种独特的动物模型（肥胖沙鼠）以及2型糖尿病易感性较高的人群（如北美印第安人和南太平洋岛民）中得到了支持。然而，在一些发展中社区（如南非黑人），围产期营养不良导致β细胞功能障碍的节俭表型假说似乎是一个更好的解释，但这仍然是一个有争议的问题。已经有几个基因被确定为节俭基因型的候选基因，包括那些编码胰岛素信号和瘦素途径蛋白以及中间脂肪代谢的基因。特别令人感兴趣的是过氧化物酶体增殖物激活受体。一种创新方法可能是关注节俭基因型的“镜像”——先天性脂肪萎缩性糖尿病，其分子缺陷仍然是个谜。我们得出结论，节俭基因型的遗传基础可能源于上述几个位点多态性的累加效应，而不是单一的调节异常。
