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cover of episode Dr. Zachary Knight: The Science of Hunger & Medications to Combat Obesity

Dr. Zachary Knight: The Science of Hunger & Medications to Combat Obesity

2024/6/17
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Huberman Lab

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A
Andrew Huberman
是一位专注于神经科学、学习和健康的斯坦福大学教授和播客主持人。
Z
Zachary Knight
Topics
Andrew Huberman: 本期节目讨论了饥饿、食欲、口渴等动机行为的科学机制,以及多巴胺、迷走神经等在其中的作用。重点关注了GLP-1及其相关药物(如Ozempic和Mounjaro)在减重方面的应用,以及这些药物的作用机制、副作用和未来发展方向。还探讨了口渴与水分摄入、钠摄入与食物摄入之间的关系,以及饮食与心态之间的联系。 Zachary Knight: 大脑控制食物摄入主要通过两个系统:短期系统(控制单次进食量)和长期系统(追踪体脂水平)。短期系统主要位于脑干,长期系统主要位于下丘脑。瘦素是脂肪组织分泌的一种激素,它向大脑发出信号,告知体脂储备水平,从而调节食欲。肥胖症患者通常存在瘦素抵抗。进食行为可分为享乐阶段(寻找食物)和消费阶段(进食)。下丘脑的AgRP神经元在享乐阶段起关键作用,而脑干神经元在消费阶段起作用。AgRP神经元在动物看到食物时会迅速降低活性,这被认为是预测即将摄入食物量的机制。许多肥胖症患者存在AgRP/POMC神经元通路中的突变,表明遗传因素在体重调节中起重要作用。遗传因素决定了体重分布,环境因素则会改变整个分布的平均值,导致整体体重增加。超加工食品更容易导致体重增加。食用单一食物会导致感官特异性饱腹感,从而减少食物摄入量。食物偏好主要由学习决定,后摄食效应会改变对食物的偏好。控制饥饿的大部分脑回路主要对卡路里敏感,而对特定营养素的敏感性则较弱,蛋白质的敏感性最强。减重后,AgRP神经元活性增强,导致饥饿感增加,这使得维持减重变得困难。GLP-1药物最初用于治疗糖尿病,其作用机制是增强胰岛素对血糖的反应。GLP-1药物主要通过作用于孤束核和后区神经元来降低食欲,这些神经元接收来自迷走神经的信号。区分GLP-1药物的药理作用和生理作用很重要,GLP-1药物的作用浓度远高于体内自然水平。GLP-1+药物是将GLP-1激动剂与其他物质结合,以增强其效果并减少副作用。多巴胺在获得食物的动机(特别是高强度工作)和学习(将线索与食物联系起来)中起作用,而不是在食物的愉悦感中起主要作用。不同的多巴胺神经元群体对来自体内的信号(如营养物质和水分)作出反应,这有助于学习食物和饮水的效果。人类在区分饥饿和口渴方面并非完美无缺,饮水可能有助于避免因口渴而进食过多。控制盐分摄入、水分摄入和卡路里摄入的系统是分开的,但脱水性厌食症表明这三者之间存在相互作用。大脑中存在对血液渗透压敏感的神经元,它们控制着对水的渴望。控制口渴的神经元会根据口腔中水的流量和血液的再水化情况来调节饮水行为。与饥饿不同,口渴更是一种不愉快的状态,动物会主动避免这种状态。控制口渴的脑回路主要位于前脑,这与控制饥饿的脑回路位置不同。大脑对营养状态的预测能力很强,外部信息会影响这种预测,从而改变对食物的感知和饱腹感。基于对食物的生理学和神经科学知识,可以制定一些简单的饮食建议来促进健康和控制体重。对抗肥胖药物领域发展前景乐观,未来会有更多药物选择,并能针对不同个体和代谢状况进行调整。

Deep Dive

Chapters
Dr. Zachary Knight discusses the two systems in the brain that control hunger and satiety: a short-term system located in the brainstem that regulates meal size and a long-term system located in the hypothalamus that tracks body fat levels and adjusts hunger accordingly. He explains that leptin, a hormone produced by fat cells, acts as a signal to the brain about the body's energy reserves. When leptin levels drop due to weight loss, the brain initiates a homeostatic response that includes increased hunger, decreased energy expenditure, and other physiological changes.

Shownotes Transcript

In this episode, my guest is Dr. Zachary Knight, Ph.D.), a professor of physiology at the University of California, San Francisco (UCSF), and Howard Hughes Medical Institute (HHMI) investigator. We discuss how the brain controls our sense of hunger, satiety, and thirst. He explains how dopamine levels impact our cravings and eating behavior (amount, food choices, etc) and how we develop and can change our food preferences and adjust how much we need to eat to feel satisfied.

We discuss factors that have led to the recent rise in obesity, such as interactions between our genes and the environment and the role of processed foods and food combinations. We also discuss the new class of medications developed for the treatment of obesity and diabetes, including the GLP-1 agonists semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro). We discuss how these medications work to promote weight loss, the source of their side effects, and the newer compounds soon to overcome some of those side effects, such as muscle loss.

Dr. Knight provides an exceptionally clear explanation for our sense of hunger, thirst, and food cravings that translates to practical knowledge to help listeners better understand their relationship to food, food choices, and meal size to improve their diet and overall health.

For show notes, including referenced articles and additional resources, please visit hubermanlab.com).

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Timestamps

00:00:00 Dr. Zachary Knight

00:02:38 Sponsors: BetterHelp, Helix Sleep & Waking Up

00:07:07 Hunger & Timescales

00:11:28 Body Fat, Leptin, Hunger

00:17:51 Leptin Resistance & Obesity

00:20:52 Hunger, Food Foraging & Feeding Behaviors, AgRP Neurons

00:30:26 Sponsor: AG1

00:32:15 Body Weight & Obesity, Genes & POMC Neurons

00:39:54 Obesity, Genetics & Environmental Factors

00:46:05 Whole Foods, Ultra-Processed Foods & Palatability

00:49:32 Increasing Whole Food Consumption, Sensory Specific Satiety & Learning

00:58:55 Calories vs. Macronutrients, Protein & Salt

01:02:23 Sponsor: LMNT

01:03:58 Challenges of Weight Loss: Hunger & Energy Expenditure

01:09:50 GLP-1 Drug Development, Semaglutide, Ozempic, Wegovy

01:19:03 GLP-1 Drugs: Muscle Loss, Appetite Reduction, Nausea

01:23:24 Pharmacologic & Physiologic Effects; GLP-1 Drugs, Additional Positive Effects

01:30:14 GLP-1-Plus Development, Tirzepatide, Mounjaro, AMG 133

01:34:49 Alpha-MSH & Pharmacology

01:40:41 Dopamine, Eating & Context

01:46:01 Dopamine & Learning, Water Content & Food

01:53:23 Salt, Water & Thirst

02:03:27 Hunger vs. Thirst

02:05:46 Dieting, Nutrition & Mindset

02:09:39 Tools: Improving Diet & Limiting Food Intake

02:14:15 Anti-Obesity Drug Development

02:17:03 Zero-Cost Support, Spotify & Apple Follow & Reviews, YouTube Feedback, Social Media, Neural Network Newsletter

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