Pinheiro Filipe, Lail Hannah, Neves João Sérgio, Negrão Rita, Wanders Desiree
Department of Nutrition, Georgia State University, 140 Decatur St SE, Atlanta, GA 30303, USA.
Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
Nutrients. 2024 Dec 17;16(24):4347. doi: 10.3390/nu16244347.
Dietary sulfur amino acid restriction (SAAR) elicits various health benefits, some mediated by fibroblast growth factor 21 (FGF21). However, research on SAAR's effects on the heart is limited and presents mixed findings. This study aimed to evaluate SAAR-induced molecular alterations associated with cardiac remodeling and their dependence on FGF21. Male C57BL/6J wild-type and FGF21 knockout mice were randomized into four dietary regimens, including normal fat and high-fat diets (HFDs) with and without SAAR, over five weeks. SAAR significantly reduced body weight and visceral adiposity while increasing serum FGF21 levels. In the heart, SAAR-induced molecular metabolic alterations are indicative of enhanced lipid utilization, glucose uptake, and mitochondrial biogenesis. SAAR also elicited opposing effects on the cardiac gene expression of FGF21 and adiponectin. Regarding cellular stress responses, SAAR mitigated the HFD-induced increase in the cardiac expression of genes involved in oxidative stress, inflammation, and apoptosis, while upregulating antioxidative genes. Structurally, SAAR did not induce alterations indicative of cardiac hypertrophy and it counteracted HFD-induced fibrotic gene expression. Overall, most alterations induced by SAAR were FGF21-independent, except for those related to lipid utilization and glucose uptake. Altogether, SAAR promotes cardiac alterations indicative of physiological rather than pathological remodeling, primarily through FGF21-independent mechanisms.
饮食中限制含硫氨基酸（SAAR）能带来多种健康益处，其中一些是由成纤维细胞生长因子21（FGF21）介导的。然而，关于SAAR对心脏影响的研究有限，且结果不一。本研究旨在评估SAAR诱导的与心脏重塑相关的分子改变及其对FGF21的依赖性。将雄性C57BL/6J野生型和FGF21基因敲除小鼠随机分为四种饮食方案，包括正常脂肪饮食和含或不含SAAR的高脂饮食（HFD），为期五周。SAAR显著降低了体重和内脏脂肪含量，同时提高了血清FGF21水平。在心脏中，SAAR诱导的分子代谢改变表明脂质利用、葡萄糖摄取和线粒体生物发生增强。SAAR还对FGF21和脂联素的心脏基因表达产生了相反的影响。在细胞应激反应方面，SAAR减轻了HFD诱导的参与氧化应激、炎症和细胞凋亡的心脏基因表达增加，同时上调了抗氧化基因。在结构上，SAAR没有诱导出表明心脏肥大的改变，并且抵消了HFD诱导的纤维化基因表达。总体而言，SAAR诱导的大多数改变不依赖于FGF21，除了那些与脂质利用和葡萄糖摄取相关的改变。总之，SAAR主要通过不依赖FGF21的机制促进心脏改变，这些改变表明是生理性而非病理性重塑。
