Biosciences Department, Institute of Health and Society, Federal University of São Paulo-UNIFESP/BS, 1015-020, Santos, São Paulo, Brazil.
College of Health, Life and Environmental Sciences, University of Worcester, Henwick Grove, WR2 6AJ, Worcester, United Kingdom.
Metab Brain Dis. 2022 Jun;37(5):1423-1434. doi: 10.1007/s11011-022-00944-3. Epub 2022 Mar 22.
The hypothalamus is a major integrating centre that controls energy homeostasis and plays a major role in hepatic glycogen (HGlyc) turnover. Not only do hypothalamic and hepatic Akt levels influence glucose homeostasis and glycogen synthesis, but exposure to high-sugar/high-fat diets (HSHF) can also lead to hypothalamic inflammation and HGlyc accumulation. HSHF withdrawal overall restores energy and glucose homeostasis, but the actual relationship between hypothalamic inflammation and HGlyc after short-term HSHF withdrawal has not yet been fully elucidated. Here we investigated the short-term effects of HSHF withdrawal preceded by a 30-day HSHF intake on the liver-hypothalamus crosstalk and glucose homeostasis. Sixty-day old male Wistar rats were fed for 30 days a control chow (n = 10) (Ct), or an HSHF diet (n = 20). On the 30th day of dietary intervention, a random HSHF subset (n = 10) had their diets switched to control chow for 48 h (Hw) whilst the remaining HSHF rats remained in the HSHF diet (n = 10) (Hd). All rats were anaesthetized and euthanized at the end of the protocol. We quantified HGlyc, Akt phosphorylation, inflammation and glucose homeostasis biomarkers. We also assessed the effect of propensity to obesity on those biomarkers, as detailed previously. Hd rats showed impaired glucose homeostasis, higher HGlyc and hypothalamic inflammation, and lower pAkt/Akt. Increased HGlyc was significantly associated with HSHF intake on pAkt/Akt lowered levels. We also found that HGlyc breakdown may have prevented a further pAkt/Akt drop after HSHF withdrawal. Propensity to obesity showed no apparent effect on hypothalamic inflammation or glucose homeostasis. Our findings suggest a comprehensive role of HGlyc as a structural and functional modulator of energy metabolism, and such roles may come into play relatively rapidly.
下丘脑是一个主要的整合中心，控制能量平衡，在肝糖原（HGlyc）周转中起主要作用。不仅下丘脑和肝 Akt 水平影响葡萄糖稳态和糖原合成，而且暴露于高糖/高脂肪饮食（HSHF）也会导致下丘脑炎症和 HGlyc 积累。HSHF 戒断总体上恢复能量和葡萄糖稳态，但短期 HSHF 戒断后下丘脑炎症和 HGlyc 之间的实际关系尚未完全阐明。在这里，我们研究了 HSHF 摄入 30 天后 HSHF 戒断对肝-下丘脑串扰和葡萄糖稳态的短期影响。60 天大的雄性 Wistar 大鼠用对照饲料（n = 10）（Ct）或 HSHF 饮食（n = 20）喂养 30 天。在饮食干预的第 30 天，随机的 HSHF 亚组（n = 10）将饮食切换为对照饲料 48 小时（Hw），而其余的 HSHF 大鼠仍留在 HSHF 饮食中（n = 10）（Hd）。所有大鼠在方案结束时麻醉并安乐死。我们量化了 HGlyc、Akt 磷酸化、炎症和葡萄糖稳态生物标志物。我们还评估了肥胖倾向对这些生物标志物的影响，如前所述。Hd 大鼠表现出葡萄糖稳态受损、HGlyc 和下丘脑炎症升高以及 pAkt/Akt 降低。HGlyc 的增加与 HSHF 摄入呈显著相关，pAkt/Akt 降低水平与 HSHF 摄入呈显著相关。我们还发现，HGlyc 分解可能阻止了 HSHF 戒断后 pAkt/Akt 的进一步下降。肥胖倾向对下丘脑炎症或葡萄糖稳态没有明显影响。我们的研究结果表明，HGlyc 作为能量代谢结构和功能调节剂具有综合作用，这种作用可能相对较快地发挥作用。
