Fink Brian D, Herlein Judy A, Almind Katrine, Cinti Saverio, Kahn C Ronald, Sivitz William I
University of Iowa, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Nov;293(5):R1773-80. doi: 10.1152/ajpregu.00478.2007. Epub 2007 Aug 29.
We quantified uncoupling proteins (UCPs) in molar amounts and assessed proton conductance in mitochondria isolated from interscapular brown adipose tissue (IBAT) and hindlimb muscle [known from prior work to contain ectopic brown adipose tissue (BAT) interspersed between muscle fibers] of obesity-resistant 129S6/SvEvTac (129) and obesity-prone C57BL/6 (B6) mice under conditions of low (LF) and high-fat (HF) feeding. With usual feeding, IBAT mitochondrial UCP1 content and proton conductance were greater in 129 mice than B6. However, with HF feeding, UCP1 and proton conductance increased more in B6 mice. Moreover, with HF feeding GDP-inhibitable proton conductance, specific for UCP1, equaled that seen in the 129 strain. UCP1 expression was substantial in mitochondria from hindlimb muscle tissue (ectopic BAT) of 129 mice as opposed to B6 but did not increase with HF feeding in either strain. As expected, muscle UCP3 expression increased with HF feeding in both strains but did not differ by strain. Moreover, the proton conductance of mitochondria isolated from hindlimb muscle tissue did not differ by strain or diet. Our data uncover a response to weight gain in obesity-prone (compared to resistant) mice unrecognized in prior studies that examined only UCP1 mRNA. Obesity-prone mice have the capacity to increase both IBAT UCP1 protein and mitochondrial proton conductance as much or more than obesity-resistant mice. But, this is only achieved only at a higher body mass and, therefore, may be adaptive rather than preventative. Neither obesity-prone nor resistant mice respond to HF feeding by expressing more UCP1 in ectopic BAT within muscle tissue.
我们对解偶联蛋白（UCPs）进行了摩尔量定量，并评估了从抗肥胖的129S6/SvEvTac（129）小鼠和易肥胖的C57BL/6（B6）小鼠的肩胛间棕色脂肪组织（IBAT）和后肢肌肉[先前的研究已知其肌肉纤维间散布着异位棕色脂肪组织（BAT）]中分离出的线粒体的质子传导率，这些小鼠分别处于低脂肪（LF）和高脂肪（HF）喂养条件下。在正常喂养时，129小鼠的IBAT线粒体UCP1含量和质子传导率高于B6小鼠。然而，在高脂肪喂养时，B6小鼠的UCP1和质子传导率增加得更多。此外，在高脂肪喂养时，对UCP1特异的GDP抑制性质子传导率与129品系中的相当。与B6小鼠相反，UCP1在129小鼠后肢肌肉组织（异位BAT）的线粒体中表达丰富，但在两种品系中，高脂肪喂养均未使其增加。正如预期的那样，两种品系中肌肉UCP3的表达均随高脂肪喂养而增加，但品系间无差异。此外，从后肢肌肉组织分离出的线粒体的质子传导率在品系或饮食方面均无差异。我们的数据揭示了在先前仅检测UCP1 mRNA的研究中未被认识到的易肥胖（与抗肥胖相比）小鼠对体重增加的反应。易肥胖小鼠增加IBAT UCP1蛋白和线粒体质子传导率的能力与抗肥胖小鼠相同或更强。但是，这仅在更高的体重时才实现，因此可能是适应性的而非预防性的。易肥胖和抗肥胖小鼠均不会通过在肌肉组织内的异位BAT中表达更多UCP1来对高脂肪喂养作出反应。
