Rossmeislová Lenka, Krauzová Eva, Koc Michal, Wilhelm Marek, Šebo Viktor, Varaliová Zuzana, Šrámková Veronika, Schouten Moniek, Šedivý Petr, Tůma Petr, Kovář Jan, Langin Dominique, Gojda Jan, Šiklová Michaela
Department of Pathophysiology, Centre for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Charles University, Prague and Université Toulouse III - Paul Sabatier (UPS), Toulouse, France.
Heliyon. 2024 Sep 14;10(18):e37875. doi: 10.1016/j.heliyon.2024.e37875. eCollection 2024 Sep 30.
Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period. Using physiological methods, lipidomics, and AT explants, we showed that obesity partially modified AT endocrine activity and blunted the dynamics of AT insulin resistance in response to the fasting/refeeding challenge compared to that observed in lean women. AT adapted to its own excess by reducing lipolytic activity/free fatty acids (FFA) flux per mass. This adaptation persisted even after a 60-h fast, resulting in lower ketosis in women with obesity. This could be a protective mechanism that limits the lipotoxic effects of FFA; however, it may ultimately impede desirable weight loss induced by caloric restriction in women with obesity.
禁食会导致底物利用发生显著变化，并出现急性胰岛素抵抗（IR）的迹象，而肥胖与慢性IR相关。尽管如此，这两种状态都会对脂肪组织（AT）功能产生重大影响。因此，在这项干预性研究（NCT04260542）中，我们研究了绝经前女性的过度肥胖是否会改变胰岛素敏感性以及AT的代谢和内分泌活动，以应对60小时禁食和随后48小时的再喂养期。通过生理学方法、脂质组学和AT外植体，我们发现与瘦女性相比，肥胖会部分改变AT的内分泌活动，并减弱AT对禁食/再喂养挑战的胰岛素抵抗动态变化。AT通过降低单位质量的脂解活性/游离脂肪酸（FFA）通量来适应自身的过量状态。即使经过60小时禁食，这种适应性仍然存在，导致肥胖女性的酮症水平较低。这可能是一种保护机制，可限制FFA的脂毒性作用；然而，它最终可能会阻碍肥胖女性因热量限制而实现的理想体重减轻。
