Cuthbertson D J, Steele T, Wilding J P, Halford J C, Harrold J A, Hamer M, Karpe F
Obesity and Endocrinology Research Group, University Hospital Aintree, Liverpool, UK.
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Int J Obes (Lond). 2017 Jun;41(6):853-865. doi: 10.1038/ijo.2017.4. Epub 2017 Jan 12.
Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease. Similar mechanistic considerations underpinning the heterogeneity of overfeeding responses are pertinent in understanding emerging metabolic phenotypes, for example, metabolically unhealthy normal weight and metabolically healthy obesity. Intrinsic and extrinsic factors modulate individuals' overfeeding response: intrinsic factors include gender/hormonal status, genetic/ethnic background, baseline metabolic health and cardiorespiratory fitness; extrinsic factors include macronutrient (fat vs carbohydrate) content, fat/carbohydrate composition and overfeeding pattern. Subcutaneous adipose tissue (SAT) analysis, coupled with metabolic assessment, with overfeeding have revealed how SAT remodels to accommodate excess nutrients. SAT remodelling occurs either by hyperplasia (increased adipocyte number) or by hypertrophy (increased adipocyte size). Biological responses of SAT also govern the extent of ectopic (visceral/liver) triglyceride deposition. Body composition analysis by DEXA/MRI (dual energy X-ray absorptiometry/magnetic resonance imaging) have determined the relative expansion of SAT (including abdominal/gluteofemoral SAT) vs ectopic fat with overfeeding. Such studies have contributed to the adipose expandability hypothesis whereby SAT has a finite capacity to expand (governed by intrinsic biological characteristics), and once capacity is exceeded ectopic triglyceride deposition occurs. The potential for SAT expandability confers protection from/predisposes to the adverse metabolic responses to overfeeding. The concept of a personal fat threshold suggests a large inter-individual variation in SAT capacity with ectopic depot expansion/metabolic decompensation once one's own threshold is exceeded. This review summarises insight gained from overfeeding studies regarding susceptibility to obesity and related complications with nutrient excess.
过度喂养实验中，我们强制实现短期正能量平衡，这有助于揭示细胞、生理和行为对营养过剩的适应性变化。这些研究模拟了长期能量消耗与摄入不匹配的情况。当暴露于相似的相对热量过剩时，体重增加幅度存在相当大的个体间异质性，这反映了代偿性适应机制的不同激活程度。重要的是，在相对体重增加相似的情况下，个体可能对代谢并发症（胰岛素抵抗、血脂异常、高血压）、非酒精性脂肪肝病和心血管疾病具有抗性或易感性。支撑过度喂养反应异质性的类似机制考量，对于理解新出现的代谢表型，例如代谢不健康的正常体重和代谢健康的肥胖，具有重要意义。内在和外在因素调节个体的过度喂养反应：内在因素包括性别/激素状态、遗传/种族背景、基线代谢健康状况和心肺适能；外在因素包括宏量营养素（脂肪与碳水化合物）含量、脂肪/碳水化合物组成以及过度喂养模式。对皮下脂肪组织（SAT）进行分析，并结合代谢评估，研究过度喂养时SAT如何重塑以适应过量营养。SAT重塑通过增生（脂肪细胞数量增加）或肥大（脂肪细胞大小增加）发生。SAT的生物学反应也决定了异位（内脏/肝脏）甘油三酯沉积的程度。通过双能X线吸收法/磁共振成像（DEXA/MRI）进行身体成分分析，已确定过度喂养时SAT（包括腹部/臀股部SAT）与异位脂肪的相对扩张情况。此类研究促成了脂肪扩张性假说，即SAT具有有限的扩张能力（由内在生物学特性决定），一旦超过该能力，就会发生异位甘油三酯沉积。SAT扩张的可能性赋予了对过度喂养不良代谢反应的抗性或易感性。个人脂肪阈值的概念表明，SAT容量存在很大个体间差异，一旦超过自身阈值，就会出现异位脂肪堆积/代谢失代偿。本综述总结了从过度喂养研究中获得的关于营养过剩时肥胖易感性及相关并发症的见解。
