Department of Psychology and Neuroscience, Temple University, Philadelphia, PA, USA.
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA; NIH-Brown University Graduate Program in Neuroscience, Bethesda, MD, USA.
Mol Metab. 2024 Nov;89:102021. doi: 10.1016/j.molmet.2024.102021. Epub 2024 Aug 30.
Exposure to 60% high fat diet (HFD) leads to a robust consummatory preference over well-balanced chow standard diet (SD) when mice are presented with a choice. This passive HFD-induced SD devaluation following HFD challenge and withdrawal is highlighted by the significant reduction in SD food intake even in states of caloric deprivation. The elements of HFD that lead to this SD depreciation remains unclear. Possibly important factors include the amount and type of fat contained in a diet as well as past eating experiences dependent on sensory properties including taste and post ingestive feedback. We aimed to explore the role of these components to HFD-induced SD devaluation.
Wildtype mice were longitudinally presented discrete HFDs in conjunction with SD and feeding and metabolic parameters were analyzed. A separate cohort of animals were assessed for acute HFD preference in 3 conditions: 1) ad libitum fed (sated), 2) overnight fasted (physiologically hungry), and 3) ad libitum fed (artificially hungry), elicited through chemogenetic Agouti-related peptide (AgRP) neuron activation. Population dynamics of AgRP neurons were recorded to distinct inaccessible and accessible diets both before and after consummatory experience. Transient receptor potential channel type M5 (TRPM5) knockout mice were used to investigate the role of fat taste perception and preference to HFD-induced SD devaluation. The clinically approved lipase inhibitor orlistat was used to test the contribution of fat absorption to HFD-induced SD devaluation.
HFD-induced SD devaluation is dependent on fat content, composition, and preference. This effect scaled both in strength and latency with higher percentages of animal fat. 60% HFD was preferred and almost exclusively consumed in preference to other diets across hours and days, but this was not as evident upon initial introduction over seconds and minutes, suggesting ingestive experience is critical. Optical fiber photometry recordings of AgRP activity supported this notion as neuronal suppression by the different diets was contingent on prior intake. While taste transduced via TRPM5 influenced HFD-evoked weight gain, it failed to impact either HFD preference or HFD-induced SD devaluation. Perturbation of post ingestive feedback through orlistat-mediated diminishment of fat absorption prevented HFD-evoked weight gain and abolished HFD-induced SD devaluation.
Post ingestive feedback via fat digestion is vital for expression of HFD-induced SD devaluation.
当给予选择时，暴露于 60%高脂肪饮食（HFD）会导致小鼠对平衡的标准饮食（SD）产生强烈的消费偏好。这种被动的 HFD 诱导的 SD 减损在 HFD 挑战和撤回后尤为明显，因为即使在卡路里剥夺的状态下，SD 食物的摄入量也会显著减少。导致这种 SD 折旧的 HFD 元素仍不清楚。可能重要的因素包括饮食中脂肪的数量和类型，以及过去的饮食经验，这些经验取决于包括味道和摄入后反馈在内的感官特性。我们旨在探讨这些成分对 HFD 诱导的 SD 减损的作用。
对野生型小鼠进行纵向呈现离散的 HFD 与 SD，并分析其喂养和代谢参数。另一组动物在 3 种条件下评估急性 HFD 偏好：1）自由喂养（饱食），2）过夜禁食（生理饥饿），3）自由喂养（人为饥饿），通过化学遗传 Agouti 相关肽（AgRP）神经元激活来诱发。在进行消费体验前后，记录 AgRP 神经元的群体动力学，以区分无法接近和可接近的饮食。使用瞬时受体电位通道型 M5（TRPM5）敲除小鼠来研究脂肪味觉感知和对 HFD 诱导的 SD 减损的偏好的作用。使用临床批准的脂肪酶抑制剂奥利司他来测试脂肪吸收对 HFD 诱导的 SD 减损的贡献。
HFD 诱导的 SD 减损取决于脂肪含量、组成和偏好。这种效应的强度和潜伏期都随着动物脂肪的百分比增加而增加。60%的 HFD 是首选的，几乎只在数小时和数天内被消耗，而在最初的几秒钟和几分钟内则不那么明显，这表明摄入经验是至关重要的。AgRP 活性的光纤光度记录支持了这一观点，因为不同饮食对神经元的抑制取决于先前的摄入。虽然通过 TRPM5 转导的味觉影响了 HFD 引起的体重增加，但它并没有影响 HFD 偏好或 HFD 诱导的 SD 减损。通过奥利司他介导的脂肪吸收减少来干扰摄入后的反馈，防止了 HFD 引起的体重增加，并消除了 HFD 诱导的 SD 减损。
通过脂肪消化进行摄入后的反馈对于表达 HFD 诱导的 SD 减损至关重要。
