饮食诱导的肥胖小鼠保留内源性瘦素作用。
Diet-induced obese mice retain endogenous leptin action.
作者信息
Ottaway Nickki, Mahbod Parinaz, Rivero Belen, Norman Lee Ann, Gertler Arieh, D'Alessio David A, Perez-Tilve Diego
机构信息
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA.
Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati, OH 45237, USA; Department of Pharmacology, University of Granada, Granada 18071, Spain.
出版信息
Cell Metab. 2015 Jun 2;21(6):877-82. doi: 10.1016/j.cmet.2015.04.015. Epub 2015 May 14.
Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.
肥胖的特征是高瘦素血症和对外源性瘦素的反应降低。这被广泛归因于瘦素抵抗的发展，瘦素抵抗是一种瘦素信号受损的状态，被认为与肥胖的发生和持续存在有关。为了直接测定肥胖状态下内源性瘦素的活性，我们用瘦素受体拮抗剂处理了瘦小鼠和肥胖小鼠。该拮抗剂增加了瘦小鼠的进食量和体重，但在瘦素、瘦素受体或黑皮质素-4受体缺乏的肥胖模型中没有这种作用。相反，该拮抗剂在瘦小鼠和饮食诱导的肥胖（DIO）小鼠中同等程度地增加了进食量和体重，这种增加与瘦素的主要靶标Socs3在下丘脑中的表达降低有关。这些发现表明，高瘦素血症的DIO小鼠保持了与瘦小鼠相当的瘦素对进食的抑制作用，反驳了对内源性瘦素的抵抗导致小鼠DIO持续存在的观点。
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