Chrobok Lukasz, Klich Jasmin D, Sanetra Anna M, Jeczmien-Lazur Jagoda S, Pradel Kamil, Palus-Chramiec Katarzyna, Kepczynski Mariusz, Piggins Hugh D, Lewandowski Marian H
Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Krakow, Poland.
Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University in Krakow, Krakow, Poland.
J Physiol. 2022 Feb;600(4):751-767. doi: 10.1113/JP281838. Epub 2021 Sep 20.
Temporal partitioning of daily food intake is crucial for survival and involves the integration of internal circadian states and external influences such as the light-dark cycle and dietary composition. These intrinsic and extrinsic factors are interdependent with misalignment of circadian rhythms promoting body weight gain, while consumption of a calorie-dense diet elevates the risk of obesity and blunts circadian rhythms. Recently, we defined the circadian properties of the dorsal vagal complex of the brainstem, a structure implicated in the control of food intake and autonomic tone, but whether and how 24 h rhythms in this area are influenced by diet remains unresolved. Here we focused on a key structure of this complex, the nucleus of the solitary tract (NTS). We used a combination of immunohistochemical and electrophysiological approaches together with daily monitoring of body weight and food intake to interrogate how the neuronal rhythms of the NTS are affected by a high-fat diet. We report that short-term consumption of a high-fat diet increases food intake during the day and blunts NTS daily rhythms in neuronal discharge. Additionally, we found that a high-fat diet dampens NTS responsiveness to metabolic neuropeptides, and decreases orexin immunoreactive fibres in this structure. These alterations occur without prominent body weight gain, suggesting that a high-fat diet acts initially to reduce activity in the NTS to disinhibit mechanisms that suppress daytime feeding. KEY POINTS: The dorsal vagal complex of the rodent hindbrain possesses intrinsic circadian timekeeping mechanisms In particular, the nucleus of the solitary tract (NTS) is a robust circadian oscillator, independent of the master suprachiasmatic clock Here, we reveal that rat NTS neurons display timed daily rhythms in their neuronal activity and responsiveness to ingestive cues These daily rhythms are blunted or eliminated by a short-term high-fat diet, together with increased consumption of calories during the behaviourally quiescent day Our results help us better understand the circadian control of satiety by the brainstem and its malfunctioning under a high-fat diet.
每日食物摄入的时间分配对生存至关重要，它涉及内部昼夜节律状态与外部影响因素（如明暗周期和饮食组成）的整合。这些内在和外在因素相互依存，昼夜节律失调会促进体重增加，而高热量饮食的摄入会增加肥胖风险并削弱昼夜节律。最近，我们确定了脑干背侧迷走神经复合体的昼夜节律特性，该结构与食物摄入和自主神经张力的控制有关，但该区域的24小时节律是否以及如何受到饮食影响仍未明确。在这里，我们聚焦于该复合体的一个关键结构，即孤束核（NTS）。我们结合免疫组织化学和电生理方法，同时每日监测体重和食物摄入量，以探究高脂肪饮食如何影响NTS的神经元节律。我们报告称，短期食用高脂肪饮食会增加白天的食物摄入量，并减弱NTS神经元放电的每日节律。此外，我们发现高脂肪饮食会减弱NTS对代谢神经肽的反应性，并减少该结构中食欲素免疫反应性纤维。这些改变在体重没有显著增加的情况下发生，表明高脂肪饮食最初通过降低NTS的活性来解除抑制白天进食的机制。要点：啮齿动物后脑的背侧迷走神经复合体具有内在的昼夜计时机制。特别是，孤束核（NTS）是一个强大的昼夜节律振荡器，独立于主视交叉上核时钟。在这里，我们揭示大鼠NTS神经元在其神经元活动和对摄食线索的反应性方面表现出定时的每日节律。这些每日节律会被短期高脂肪饮食减弱或消除，同时在行为静止的白天热量消耗增加。我们的研究结果有助于我们更好地理解脑干对饱腹感的昼夜控制及其在高脂肪饮食下的功能失调。
