Sexually dimorphic role of diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus.
Sexually dimorphic role of diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus.
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饮食和压力对行为、能量代谢和腹内侧下丘脑的性别二态性作用。
DOI：
10.1101/2023.11.17.567534
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Rajbhandari,AbhaK
中科院分区：
文献类型：
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作者：
Shetty,Sanutha;Duesman,SamuelJ;Patel,Sanil;Huyhn,Pacific;Shroff,Sanjana;Das,Anika;Chowhan,Disha;Sebra,Robert;Beaumont,Kristin;McAlpine,CameronS;Rajbhandari,Prashant;Rajbhandari,AbhaK
科学证据强调了生理性别对压力和代谢功能障碍之间相互作用的影响。然而，对于饮食和压力如何共同导致男性和女性的代谢失调的理解有限。为了解决这一差距，我们的研究旨在研究高脂饮食（HFD）和重复足电击应激对雄性和雌性小鼠恐惧相关行为和代谢结果的综合影响。使用一个强大的啮齿动物模型，概括创伤后应激障碍（PTSD）的关键方面，我们对小鼠进行足电击应激源，然后每周提醒足电击应激源或无应激源，持续14周，而无论是HFD或食物饮食。我们的研究结果表明，HFD损害了接受初始应激的雄性小鼠的恐惧记忆消退，但在雌性小鼠中没有。血糖水平受饮食和性别的影响，HFD喂养的雌性小鼠显示出升高的水平，在没有压力的情况下恢复到基线，这在雄性小鼠中没有观察到。HFD的雄性小鼠表现出更高的能量消耗，而HFD喂养的雌性小鼠表现出降低的呼吸交换率（RER）。在接受HFD的慢性应激小鼠的不同外周组织中观察到促炎标志物和造血干细胞丰度的性别特异性改变，表明存在不同的共病疾病。HFD应激小鼠下丘脑腹内侧单核RNA测序提供了性别特异性胶质细胞活化和细胞类型特异性转录组学变化的见解。总之，我们的研究提供了对压力，饮食，性以及各种生理和行为结果之间复杂相互作用的全面理解，揭示了协调这些相互作用的潜在大脑区域。
Scientific evidence underscores the influence of biological sex on the interplay between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress jointly contribute to metabolic dysregulation in both males and females. To address this gap, our study aimed to investigate the combined effects of a high-fat diet (HFD) and repeated footshock stress on fear-related behaviors and metabolic outcomes in male and female mice. Using a robust rodent model that recapitulates key aspects of post-traumatic stress disorder (PTSD), we subjected mice to footshock stressor followed by weekly reminder footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. Our findings revealed that HFD impaired fear memory extinction in male mice that received initial stressor but not in female mice. Blood glucose levels were influenced by both diet and sex, with HFD-fed female mice displaying elevated levels that returned to baseline in the absence of stress, a pattern not observed in male mice. Male mice on HFD exhibited higher energy expenditure, while HFD-fed female mice showed a decreased respiratory exchange ratio (RER). Sex-specific alterations in pro-inflammatory markers and abundance of hematopoietic stem cells were observed in chronically stressed mice on an HFD in different peripheral tissues, indicating the manifestation of distinct comorbid disorders. Single-nuclei RNA sequencing of the ventromedial hypothalamus from stressed mice on an HFD provided insights into sex-specific glial cell activation and cell-type-specific transcriptomic changes. In conclusion, our study offers a comprehensive understanding of the intricate interactions between stress, diet, sex, and various physiological and behavioral outcomes, shedding light on a potential brain region coordinating these interactions.