Impaired leptin responsiveness in aged rats
Impaired leptin responsiveness in aged rats
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DOI：
10.2337/diabetes.49.3.431
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发表时间：
2000-03-01
期刊：
影响因子：
7.7
通讯作者：
Tümer, N
中科院分区：
文献类型：
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作者：
Scarpace, PJ;Matheny, M;Tümer, N
我们之前报道过，雄性F-344 × BN大鼠的肥胖和血清瘦素水平随着年龄的增长而增加，当空腹控制血清瘦素的生理水平时，年轻大鼠的下丘脑神经肽Y (NPY) mRNA会发生相应的相互变化，但在老年大鼠中没有变化。这些发现表明，瘦素对下丘脑NPY mRNA的调节可能随着年龄的增长而受损。为了验证这一假设，我们将生理盐水或瘦素注入自由喂养的大鼠7天，并将这些大鼠与生理盐水注入的大鼠进行比较，这些大鼠的食物摄取量与瘦素治疗大鼠的食物摄取量相同。我们检测了每日食物摄入量、体重、全身耗氧量、血清瘦素和下丘脑NPY mRNA。注射瘦素的老鼠食量比注射盐水的老鼠减少了50%，而老年老鼠只减少了20%。在瘦素治疗的年轻大鼠中，与成对喂养的大鼠相比，氧气消耗增加了24%，但老年大鼠的氧气消耗没有变化。与配对喂养的年轻大鼠相比，瘦素输注使下丘脑NPY水平降低了近50%，而衰老大鼠下丘脑NPY mRNA水平没有变化。总之，老龄大鼠对瘦素的反应降低，包括食物摄入量减少，能量消耗不增加。这些对瘦素的反应减弱与下丘脑NPY mRNA水平抑制受损有关，也可能是下丘脑NPY mRNA水平抑制受损的结果。这种瘦素抵抗可能是由于肥胖和血清瘦素随着年龄的增长而升高，或由于年龄本身，或两者兼而有之。
We previously reported that adiposity and serum leptin levels increase with age in male F-344 x BN rats and that when physiological levels of serum leptin are manipulated by fasting, there is a corresponding reciprocal change in hypothalamic neuropeptide Y (NPY) mRNA in young rats, but there are no changes in older rats. These findings suggest that the regulation of hypothalamic NPY mRNA by leptin may be impaired with age. To test this hypothesis, we infused saline or leptin for 7 days into ad libitum-fed rats and compared these with saline-infused rats that were pair-fed the amount of food consumed by the leptin-treated rats. We examined daily food consumption, body weight, whole-body oxygen consumption, serum leptin, and NPY mRNA in the hypothalamus. Food consumption decreased by 50% in the leptin-infused compared with the saline-infused young rats but only decreased by 20% in the aged rats. In the leptin-treated young rats, there was a 24% increase in oxygen consumption compared with the pair-fed rats, but there were no changes in oxygen consumption in the aged rats. Leptin infusion diminished hypothalamic NPY levels by nearly 50% compared with pair-fed young rats, whereas there were no changes in the hypothalamic NPY mRNA levels in senescent rats. In summary, aged rats demonstrate a reduced responsiveness to leptin, including a diminished decrease in food intake and no increase in energy expenditure. These diminished responses to leptin were associated with and may be the result of an impaired suppression of hypothalamic NPY mRNA levels. This leptin resistance may be due to either the elevated obesity and serum leptin with age or due to age itself, or both.