Section of Endocrinology, Diabetes and Weight Management, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Odessa, TX, USA.
Metabolism. 2018 Sep;86:18-32. doi: 10.1016/j.metabol.2017.11.006. Epub 2017 Nov 16.
The understanding of adipose tissue role has evolved from that of a depot energy storage organ to a dynamic endocrine organ. While genetics, sexual phenotype and sex steroids can impact the mass and distribution of adipose tissue, there is a counter-influence of white adipocytes on reproduction. This primarily occurs via the secretion of adipokines, the most studied of which- leptin and adiponectin- are highlighted in this article. Leptin, the "satiety hormone" primarily acts on the hypothalamus via pro-opiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AgRP) neurons to translate acute changes in nutrition and energy expenditure, as well as chronic adipose accumulation into changes in appetite and potentially mediate insulin resistance via shared pathway and notably impacting reproductive health via influence on GnRH secreting neurons. Meanwhile, adiponectin is notable for its action in mediating insulin sensitivity, with receptors found at every level of the reproductive axis. Both have been examined in the context of physiologic and pathologic reproductive conditions. Leptin has been shown to influence puberty, pregnancy, hypothalamic amenorrhea, and lipodystrophy, and with a potential therapeutic role for both metabolic and reproductive health. Adiponectin mediates the relative state of insulin resistance in pregnancy, and has been implicated in conditions such as polycystic ovary syndrome and reproductive malignancies. There are numerous other adipokines, including resistin, visfatin, chemerin and retinol binding protein-4, which may also play roles in reproductive health and disease states. The continued examination of these and other adipokines in both normal reproduction and reproductive pathologies represents an important avenue for continued study. Here, we seek to provide a broad, yet comprehensive overview of many facets of these relationships and highlight areas of consideration for clinicians and future study.
人们对脂肪组织作用的认识已经从储存能量的器官发展为一个活跃的内分泌器官。虽然遗传、性表型和性激素会影响脂肪组织的质量和分布,但白色脂肪细胞对生殖也有反作用。这种反作用主要通过脂肪因子的分泌来实现,其中研究最多的是瘦素和脂联素,本文对此进行了重点介绍。瘦素作为“饱腹感激素”,主要通过前阿黑皮素原(POMC)、神经肽 Y(NPY)和刺鼠相关蛋白(AgRP)神经元作用于下丘脑,将营养和能量消耗的急性变化以及慢性脂肪堆积转化为食欲变化,并通过共享途径潜在介导胰岛素抵抗,尤其通过对 GnRH 分泌神经元的影响,对生殖健康产生影响。与此同时,脂联素以其调节胰岛素敏感性的作用而引人注目,其受体存在于生殖轴的各个水平。这两种激素都在生理和病理生殖条件下进行了研究。瘦素已被证明会影响青春期、妊娠、下丘脑性闭经和脂肪营养不良,并且具有代谢和生殖健康的潜在治疗作用。脂联素介导妊娠时胰岛素抵抗的相对状态,并与多囊卵巢综合征和生殖恶性肿瘤等疾病有关。还有许多其他脂肪因子,包括抵抗素、内脏脂肪素、趋化因子和视黄醇结合蛋白-4,它们也可能在生殖健康和疾病状态中发挥作用。继续研究这些脂肪因子和其他脂肪因子在正常生殖和生殖病理中的作用,是一个重要的研究方向。在这里,我们试图提供一个广泛而全面的概述,介绍这些关系的许多方面,并强调临床医生和未来研究需要考虑的领域。