Barazzoni Rocco, Zanetti Michela, Bosutti Alessandra, Biolo Gianni, Vitali-Serdoz Laura, Stebel Marco, Guarnieri Gianfranco
Clinica Medica, University of Trieste, Ospedale Cattinara, Strada di Fiume 447, 34100 Trieste, Italy.
Endocrinology. 2005 Apr;146(4):2098-106. doi: 10.1210/en.2004-1396. Epub 2004 Dec 23.
The study aimed at determining, in lean tissues from nonobese rats, whether physiological hyperleptinemia with leptin-induced reduced caloric intake and/or calorie restriction (CR) per se: 1) enhance mitochondrial-energy metabolism gene transcript levels and oxidative capacity; and 2) reduce triglyceride content. Liver and skeletal muscles were collected from 6-month-old Fischer 344 rats after 1-wk leptin sc infusion (0.4 mg/kg . d: leptin + approximately 3-fold leptinemia vs. ad libitum-fed control) or moderate CR (-26% of those fed ad libitum) in pair-fed animals (CR). After 1 wk: 1) leptin and CR comparably enhanced transcriptional expression of mixed muscle mitochondrial genes (P < 0.05 vs. control); 2) CR independently increased (P < 0.05 vs. leptin-control) hepatic mitochondrial-lipooxidative gene expression and oxidative capacity; 3) hepatic but not muscle mitochondrial effects of CR were associated (P < 0.01) with increased activated insulin signaling at AKT level (P < 0.05 vs. leptin-control); 4) liver and muscle triglyceride content were comparable in all groups. In additional experiments, assessing time course of posttranscriptional CR effects, 3-wk superimposable CR (P < 0.05): 1) increased both liver and muscle mitochondrial oxidative capacity; and 2) selectively reduced muscle triglyceride content. Thus, in nonobese adult rat: 1) moderate CR induces early increments of mitochondrial-lipooxidative gene expression and time-dependent increments of oxidative capacity in liver and mixed muscle; 2) sustained moderate CR alters tissue lipid distribution reducing muscle but not liver triglycerides; 3) mitochondrial-lipid metabolism changes are tissue-specifically associated with hepatic AKT activation; 4) short-term physiological hyperleptinemia has no independent stimulatory effects on muscle and liver mitochondrial-lipooxidative gene expression. Increased lean tissue oxidative capacity could favor substrate oxidation over storage during reduced nutrient availability.
本研究旨在确定，在非肥胖大鼠的瘦组织中，生理性高瘦素血症伴瘦素诱导的热量摄入减少和/或热量限制（CR）本身是否：1）提高线粒体能量代谢基因转录水平和氧化能力；2）降低甘油三酯含量。从6月龄的Fischer 344大鼠收集肝脏和骨骼肌，这些大鼠在接受1周的瘦素皮下输注（0.4 mg/kg·d：瘦素+约3倍的瘦素血症，与自由进食对照相比）或成对喂养动物的中度CR（-26%自由进食量，即CR组）后。1周后：1）瘦素和CR同等程度地增强混合肌线粒体基因的转录表达（与对照相比，P<0.05）；2）CR独立增加肝脏线粒体脂氧化基因表达和氧化能力（与瘦素对照相比，P<0.05）；3）CR对肝脏而非肌肉线粒体的影响与AKT水平激活的胰岛素信号增加相关（P<0.01，与瘦素对照相比，P<0.05）；4）所有组的肝脏和肌肉甘油三酯含量相当。在额外的实验中，评估转录后CR效应的时间进程，3周可叠加的CR（P<0.05）：1）增加肝脏和肌肉线粒体氧化能力；2）选择性降低肌肉甘油三酯含量。因此，在非肥胖成年大鼠中：1）中度CR诱导肝脏和混合肌中线粒体脂氧化基因表达的早期增加以及氧化能力的时间依赖性增加；2）持续的中度CR改变组织脂质分布，降低肌肉而非肝脏甘油三酯；3）线粒体脂质代谢变化与肝脏AKT激活存在组织特异性关联；4）短期生理性高瘦素血症对肌肉和肝脏线粒体脂氧化基因表达无独立刺激作用。在营养可利用性降低期间，瘦组织氧化能力增加可能有利于底物氧化而非储存。
