Jimenez-Chillaron J C, Hernandez-Valencia M, Lightner A, Faucette R R, Reamer C, Przybyla R, Ruest S, Barry K, Otis J P, Patti M E
Department of Cellular and Molecular Physiology, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA.
Diabetologia. 2006 Aug;49(8):1974-84. doi: 10.1007/s00125-006-0311-7. Epub 2006 Jun 8.
AIMS/HYPOTHESIS: Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences.
We used our previously described mouse model of LBW-associated diabetes, created by restricting maternal food intake to 50% during the last week of gestation. Control (C) dams and dams that had been subjected to undernutrition (U) were then provided either chow ad libitum after delivery or 50% food restriction on a per-day basis from delivery until weaning. We designated the resulting four groups control-control (CC), undernutrition-control (UC), control-undernutriton (CU) and undernutrition-undernutrition (UU), indicating the prenatal and postnatal experimental conditions, respectively. Carbohydrate metabolism and adiposity were assessed prospectively in offspring until age 6 months.
Males that were small at birth and exhibited early postnatal catch-up growth developed glucose intolerance and obesity by age 6 months. In contrast, LBW mice without catch-up growth (UU) remained smaller than controls (CC), and glucose intolerance and obesity was prevented. Similarly, mice with normal birthweight that had blunted catch-up growth (CU) were leaner and had better tolerance test than CC mice. Catch-up growth during the first week of life correlated better than birthweight with glucose, fat mass and glucose tolerance up to 6 months of age.
CONCLUSIONS/INTERPRETATION: Prevention of early catch-up growth reversed the development of glucose intolerance and obesity in our mouse model of LBW-associated diabetes.
目的/假设：低出生体重（LBW）和出生后快速体重增加，即追赶性生长，是成年期肥胖和糖尿病发生的独立危险因素。出生时体型小且出生后有追赶性生长的个体风险最高。我们假设，旨在减轻低出生体重个体追赶性生长的饮食干预可能会产生长期有益影响。
我们使用了之前描述的与低出生体重相关糖尿病的小鼠模型，该模型通过在妊娠最后一周将母体食物摄入量限制为50%来创建。然后，给对照（C）组母鼠和经历过营养不良（U）的母鼠在分娩后随意提供普通饲料，或者从分娩到断奶期间每天限制50%的食物摄入量。我们将由此产生的四组分别命名为对照-对照（CC）组、营养不良-对照（UC）组、对照-营养不良（CU）组和营养不良-营养不良（UU）组，分别表示产前和产后的实验条件。对后代直至6月龄时的碳水化合物代谢和肥胖情况进行前瞻性评估。
出生时体型小且出生后早期有追赶性生长的雄性小鼠在6月龄时出现葡萄糖不耐受和肥胖。相比之下，没有追赶性生长的低出生体重小鼠（UU）仍然比对照组（CC）小，并且预防了葡萄糖不耐受和肥胖。同样，出生体重正常但追赶性生长减弱的小鼠（CU）比CC组小鼠更瘦，糖耐量测试结果更好。出生后第一周的追赶性生长与6月龄时的血糖、脂肪量和葡萄糖耐量的相关性比出生体重更好。
结论/解读：在我们的低出生体重相关糖尿病小鼠模型中，预防早期追赶性生长可逆转葡萄糖不耐受和肥胖的发展。
