College of Health Sciences, University of Memphis, Memphis, TN 38152, USA.
Int J Mol Sci. 2023 Jul 15;24(14):11492. doi: 10.3390/ijms241411492.
Glucocorticoids (GCs) are some of the most widely prescribed therapies for treating numerous inflammatory diseases and multiple cancer types. With chronic use, GCs' therapeutic benefits are concurrent with deleterious metabolic side effects, which worsen when combined with a high-fat diet (HFD). One characteristic of the common Western HFD is the presence of high omega-6 polyunsaturated fatty acids (PUFAs) and a deficiency in omega-3 PUFAs. The aim of this experiment was to determine whether fat composition resulting from HFD affects glucocorticoid-induced alterations in lipid-handling by the liver and skeletal muscle. Male wild-type C57BL/6 mice were randomized into two groups: n-6 (45% fat 177.5 g lard) and n-3 (45% fat 177.5 g Menhaden oil). After 4 weeks on their diets, groups were divided to receive either daily injections of dexamethasone (3 mg/kg/day) or sterile PBS for 1 week while continuing diets. The n-3 HFD diet attenuated adipose and hepatic fatty accumulation and prevented GC-induced increases in liver lipid metabolism markers and . N-3 HFD had little effect on markers of lipid metabolism in oxidative and glycolytic skeletal muscle and was unable to attenuate GC-induced gene expression in the muscle. The present study's result demonstrated that the change of fat composition in HFD could beneficially alter the fatty acid accumulation and associated lipid metabolism markers in mice treated with dexamethasone.
糖皮质激素（GCs）是治疗多种炎症性疾病和多种癌症类型的最广泛应用的治疗方法之一。长期使用时，GCs 的治疗益处与有害的代谢副作用并存，如果与高脂肪饮食（HFD）结合使用，副作用会加重。常见的西方 HFD 的一个特点是含有高含量的ω-6 多不饱和脂肪酸（PUFAs）和ω-3 PUFAs 的缺乏。本实验旨在确定 HFD 引起的脂肪组成是否会影响糖皮质激素诱导的肝脏和骨骼肌脂质处理的改变。雄性野生型 C57BL/6 小鼠随机分为两组：n-6（45%脂肪 177.5 g 猪油）和 n-3（45%脂肪 177.5 g 鲱鱼油）。在他们的饮食上进行了 4 周后，两组分别接受每天 3 毫克/千克/天的地塞米松（3 mg/kg/day）或无菌 PBS 注射 1 周，同时继续饮食。n-3 HFD 饮食减轻了脂肪和肝脏脂肪堆积，并防止 GC 诱导的肝脂质代谢标志物和增加。n-3 HFD 对氧化和糖酵解骨骼肌中的脂质代谢标志物几乎没有影响，并且不能减轻 GC 诱导的肌肉中的基因表达。本研究的结果表明，HFD 中脂肪组成的变化可以有益地改变用地塞米松治疗的小鼠中的脂肪酸积累和相关的脂质代谢标志物。
