出生后脂肪分泌的瘦素激增是小鼠脂肪量轨迹的有力预测因素。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Olga Horakova, Petra Janovska, Ilaria Irodenko, Jana Buresova, Inge van der Stelt, Sara Stanic, Eliska Haasova, Nivasini Shekhar, Tatyana Kobets, Jaap Keijer, Petr Zouhar, Martin Rossmeisl, Jan Kopecky, Kristina Bardova
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引用次数: 0

摘要

啮齿类动物出生后循环中瘦素水平的瞬时增加,即瘦素激增,可能会增加日后饮食诱发肥胖的易感性。然而,在瘦素激增期间瘦素的来源需要更好地确定,而且瘦素的长期影响也是相互矛盾的。需要确定瘦素与遗传背景、性别和其他因素的相互作用。在这里,我们重点研究了在2周龄和4周龄(i)易肥胖的C57BL/6(B6)小鼠和(ii)抗肥胖的A/J小鼠中测量的循环瘦素水平和几个相关变量的影响。总共使用了 264 只雌雄小鼠。皮下白色脂肪组织是小鼠幼崽最大的脂肪组织库,其转录后控制的瘦素分泌是决定血浆瘦素水平的主要因素。当小鼠在12-24周龄期间随机分配标准饲料或高脂饮食(HFD)时,在B6小鼠中观察到了高脂饮食的致肥效应,而在A/J小鼠中没有观察到。只有2周时的瘦素水平(即接近出生后瘦素激增的最大值)与24周龄小鼠一生的体重(BW)轨迹和脂肪含量相关。瘦素激增分别解释了 B6 小鼠体重和脂肪含量变异的 13% 和 7%,分别解释了 A/J 小鼠体重和脂肪含量变异的 9% 和 35%,性别的作用较小。我们的研究结果证明了瘦素激增与成年期脂肪含量之间的正相关性,反映了瘦素的基本生物学作用。这种作用在肥胖者身上可能会受到损害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Postnatal surge of adipose-secreted leptin is a robust predictor of fat mass trajectory in mice.

The transient postnatal increase in circulating leptin levels, known as leptin surge, may increase later susceptibility to diet-induced obesity in rodents. However, the source of leptin during the surge needs to be better characterized, and the long-term effects of leptin are contradictory. Characterization of the interaction of leptin with the genetic background, sex, and other factors is required. Here, we focused on the impact of circulating leptin levels and several related variables, measured in 2- and 4-week-old (i) obesity-prone C57BL/6 (B6) and (ii) obesity-resistant A/J mice. In total, 264 mice of both sexes were used. Posttranscriptionally controlled leptin secretion from subcutaneous white adipose tissue, the largest adipose tissue depot in mice pups, was the primary determinant of plasma leptin levels. When the animals were randomly assigned standard chow or high-fat diet (HFD) between 12 - 24 weeks of age, the obesogenic effect of HFD-feeding was observed in B6 but not A/J mice. Only leptin levels at 2 weeks, i.e., close to the maximum in the postnatal leptin surge, correlated with both body weight (BW) trajectory throughout the life and adiposity of the 24-week-old mice. Leptin surge explained 13 and 7 % of the variance in BW and adiposity of B6 mice and 9 and 35 % of the variance in these parameters in A/J mice, with a minor role of sex. Our results prove the positive correlation between the leptin surge and adiposity in adulthood, reflecting the fundamental biological role of leptin. This role could be compromised in obese subjects.

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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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