Cell-Specific "Competition for Calories" Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals.
Cell-Specific "Competition for Calories" Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals.
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DOI：
10.3389/fphys.2018.01053
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发表时间：
2018
影响因子：
4
通讯作者：
Hill JO
中科院分区：
文献类型：
--
作者：
Archer E;Pavela G;McDonald S;Lavie CJ;Hill JO
哺乳动物的身体是一个复杂的生理“生态系统”，其中细胞为卡路里（即营养能量）而竞争。显然，具有竞争优势的细胞类型获得更多的消耗卡路里，并且在可能的情况下，增加大小和/或数量。因此，假设肥胖是脂肪细胞（脂肪细胞）的竞争优势导致营养能量的不成比例的获取和储存，这是合乎逻辑且简洁的。因此，我们引入了两个概念框架。不对称营养能量分配描述了环境依赖的、细胞特异性的卡路里竞争，决定了营养能量分配到氧化、合成代谢和/或储存；有效卡路里摄入量描述了通过抑制肝脏和大脑中控制摄入行为的感觉运动食欲细胞来限制能量摄入的卡路里数量。在这些框架中固有的是代谢的能量需求和启动摄取行为和能量摄入的神经-肌肉途径的独立性和分离性。正如我们所证明的那样，如果感觉运动细胞通过与其他细胞类型（如骨骼肌细胞或脂肪细胞）的不对称竞争而遭受相对的热量剥夺，能量摄入就会增加，以补偿能量稳态中真实的和仅仅是表面上的缺陷（即分别为真信号和假信号）。因此，我们假设导致肥胖和代谢疾病的慢性正能量平衡（即营养过剩）是由细胞间对卡路里的不对称竞争和伴随的营养能量存储的差异分配所驱动的明显缺陷（即错误信号）造成的。这些框架与我们之前的理论工作——母体资源假说——相一致，为人类和其他哺乳动物（包括伴侣动物、家养动物、实验室动物和野生动物）中体重和脂肪量增加以及相关代谢功能障碍的全球患病率的迅速上升提供了一个简洁而严谨的解释。
The mammalian body is a complex physiologic “ecosystem” in which cells compete for calories (i.e., nutrient-energy). Axiomatically, cell-types with competitive advantages acquire a greater number of consumed calories, and when possible, increase in size and/or number. Thus, it is logical and parsimonious to posit that obesity is the competitive advantages of fat-cells (adipocytes) driving a disproportionate acquisition and storage of nutrient-energy. Accordingly, we introduce two conceptual frameworks. Asymmetric Nutrient-Energy Partitioning describes the context-dependent, cell-specific competition for calories that determines the partitioning of nutrient-energy to oxidation, anabolism, and/or storage; and Effective Caloric Intake which describes the number of calories available to constrain energy-intake via the inhibition of the sensorimotor appetitive cells in the liver and brain that govern ingestive behaviors. Inherent in these frameworks is the independence and dissociation of the energetic demands of metabolism and the neuro-muscular pathways that initiate ingestive behaviors and energy intake. As we demonstrate, if the sensorimotor cells suffer relative caloric deprivation via asymmetric competition from other cell-types (e.g., skeletal muscle- or fat-cells), energy-intake is increased to compensate for both real and merely apparent deficits in energy-homeostasis (i.e., true and false signals, respectively). Thus, we posit that the chronic positive energy balance (i.e., over-nutrition) that leads to obesity and metabolic diseases is engendered by apparent deficits (i.e., false signals) driven by the asymmetric inter-cellular competition for calories and concomitant differential partitioning of nutrient-energy to storage. These frameworks, in concert with our previous theoretic work, the Maternal Resources Hypothesis, provide a parsimonious and rigorous explanation for the rapid rise in the global prevalence of increased body and fat mass, and associated metabolic dysfunctions in humans and other mammals inclusive of companion, domesticated, laboratory, and feral animals.
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影响因子：
4.5
作者：
Ahmad S;Rukh G;Varga TV;Ali A;Kurbasic A;Shungin D;Ericson U;Koivula RW;Chu AY;Rose LM;Ganna A;Qi Q;Stančáková A;Sandholt CH;Elks CE;Curhan G;Jensen MK;Tamimi RM;Allin KH;Jørgensen T;Brage S;Langenberg C;Aadahl M;Grarup N;Linneberg A;Paré G;InterAct Consortium;DIRECT Consortium;Magnusson PK;Pedersen NL;Boehnke M;Hamsten A;Mohlke KL;Pasquale LT;Pedersen O;Scott RA;Ridker PM;Ingelsson E;Laakso M;Hansen T;Qi L;Wareham NJ;Chasman DI;Hallmans G;Hu FB;Renström F;Orho-Melander M;Franks PW
通讯作者：
Franks PW
DOI：
10.1016/j.bbrc.2010.02.165
发表时间：
2010-05-21
影响因子：
3.1
作者：
Arner, Peter;Spalding, Kirsty L.
通讯作者：
Spalding, Kirsty L.
影响因子：
8.9
作者：
Archer, Edward;Hand, Gregory A.;Blair, Steven N.
通讯作者：
Blair, Steven N.
影响因子：
2.9
作者：
Asakura, A;Komaki, M;Rudnicki, MA
通讯作者：
Rudnicki, MA
影响因子：
9.8
作者：
ARNER, P;BOLINDER, J;OSTMAN, J
通讯作者：
OSTMAN, J