Raff Hershel, Hainsworth Keri R, Woyach Victoria L, Weihrauch Dorothee, Wang Xuemeng, Dean Caron
Division of Endocrinology and Molecular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Am J Physiol Regul Integr Comp Physiol. 2024 Aug 1;327(2):R123-R132. doi: 10.1152/ajpregu.00082.2024. Epub 2024 May 23.
Obesity in adolescence is increasing in frequency and is associated with elevated proinflammatory cytokines and chronic pain in a sex-dependent manner. Dietary probiotics may mitigate these detrimental effects of obesity. Using a Long-Evans adolescent and adult rat model of overweight (high-fat diet (HFD) - 45% kcal from fat from weaning), we determined the effect of a single-strain dietary probiotic [ 299v (Lp299v) from weaning] on the theoretically increased neuropathic injury-induced pain phenotype and inflammatory cytokines. We found that although HFD increased fat mass, it did not markedly affect pain phenotype, particularly in adolescence, but there were subtle differences in pain in adult male versus female rats. The combination of HFD and Lp299v augmented the increase in leptin in adolescent females. There were many noninteracting main effects of age, diet, and probiotic on an array of cytokines and adipokines with adults being higher than adolescents, HFD higher than the control diet, and a decrease with probiotic compared with placebo. Of particular interest were the probiotic-induced increases in IL12p70 in female adolescents on an HFD. We conclude that a more striking pain phenotype could require a higher and longer duration caloric diet or a different etiology of pain. A major strength of our study was that a single-strain probiotic had a wide range of inhibiting effects on most proinflammatory cytokines. The positive effect of the probiotic on leptin in female adolescent rats is intriguing and worthy of exploration. A single-strain probiotic (Lp299v) had a wide range of inhibiting effects on most proinflammatory cytokines (especially IL12p70) measured in this high-fat diet rat model of mild obesity. The positive effect of probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.
青少年肥胖的发生率正在上升,并且以性别依赖的方式与促炎细胞因子升高和慢性疼痛相关。膳食益生菌可能减轻肥胖的这些有害影响。我们使用超重的Long-Evans青少年和成年大鼠模型(高脂饮食(HFD) - 从断奶起脂肪提供45%的千卡热量),确定了单一菌株膳食益生菌[从断奶起的299v(Lp299v)]对理论上增加的神经性损伤诱导的疼痛表型和炎性细胞因子的影响。我们发现,虽然高脂饮食增加了脂肪量,但它并未显著影响疼痛表型,尤其是在青少年中,但成年雄性和雌性大鼠在疼痛方面存在细微差异。高脂饮食和Lp299v的组合增强了青春期雌性大鼠瘦素的增加。年龄、饮食和益生菌对一系列细胞因子和脂肪因子有许多非相互作用的主要影响,成年人高于青少年,高脂饮食高于对照饮食,与安慰剂相比,益生菌使其降低。特别令人感兴趣的是,高脂饮食的青春期雌性大鼠中益生菌诱导的IL12p70增加。我们得出结论,更显著的疼痛表型可能需要更高热量且持续时间更长的饮食或不同的疼痛病因。我们研究的一个主要优势是单一菌株益生菌对大多数促炎细胞因子具有广泛的抑制作用。益生菌对雌性青春期大鼠瘦素的积极作用很有趣,值得探索。单一菌株益生菌(Lp299v)对这种轻度肥胖的高脂饮食大鼠模型中测量的大多数促炎细胞因子(尤其是IL12p70)具有广泛的抑制作用。益生菌对雌性青春期大鼠瘦素的积极作用很有趣,值得探索。