Department of Physiology and Biophysics, School of Medicine, University of California at Irvine, Irvine, California, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1259-66. doi: 10.1152/ajpregu.00397.2011. Epub 2011 Sep 14.
Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca(2+)-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.
维持 10%或更大幅度的体重减轻会导致低水平体力活动的能量消耗降低，而这种降低超出了体重变化的影响。非休息状态能量消耗的这些变化主要归因于体重减轻后骨骼肌工作效率的提高，并且可以通过给予脂肪细胞衍生的激素瘦素来逆转。我们之前还表明，维持体重减轻会伴随着股外侧肌中糖酵解（磷酸果糖激酶）与氧化（细胞色素 c 氧化酶）活性比值的降低，这表明肌球蛋白重链 I（MHC I）同工型的相对表达增加。我们对股外侧肌活检样本进行了分析，以确定维持体重改变是否与骨骼肌代谢特性的变化以及不同 MHC 同工型和肌浆内质网 Ca(2+)-依赖性 ATP 酶（SERCA）的 mRNA 表达有关，这些变化发生在研究对象减肥前，然后在体重减轻 10%并接受每日两次安慰剂或替代瘦素注射的情况下再次进行研究，采用单盲交叉设计。我们发现，维持体重减轻与 MHC I mRNA 的相对基因表达显著增加有关，而瘦素的给予可以逆转这种增加，并且 SERCA2 的表达增加，而瘦素对其没有显著影响。与接受安慰剂的受试者相比，瘦素的给予还导致 MHC IIx 同工型的表达显著增加。这些发现与饮食减肥后观察到的瘦素可逆转的骨骼肌化学机械工作效率增加和糖酵解/氧化酶活性比值降低一致。
