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Obesity changes the brain, with ‘no sign of reversibility,’ expert says
Obesity may damage the brain’s ability to recognize the sensation of fullness and be satisfied after eating fats and sugars, a new study found.
Further, those brain changes may last even after people considered medically obese lose a significant amount of weight — possibly explaining why many people often regain the pounds they lose.
“There was no sign of reversibility — the brains of people with obesity continued to lack the chemical responses that tell the body, ‘OK, you ate enough,’” said Dr. Caroline Apovian, a professor of medicine at Harvard Medical School and codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston.
As defined medically, people with obesity have a body mass index, or BMI, of over 30, while normal weight is a BMI of between 18 and 25.
“This study captures why obesity is a disease — there are actual changes to the brain,” said Apovian, who was not involved in the study.
“The study is very rigorous and quite comprehensive,” said Dr. I. Sadaf Farooqi, a professor of metabolism and medicine at the University of Cambridge in the UK, who was not involved in the new research.
The study, published Monday in Nature Metabolism, was a controlled clinical trial in which 30 people considered to be medically obese and 30 people of normal weight were fed sugar carbohydrates (glucose), fats (lipids) or water (as a control). Each group of nutrients were fed directly into the stomach via a feeding tube on separate days.
“We wanted to bypass the mouth and focus on the gut-brain connection, to see how nutrients affect the brain independently from seeing, smelling or tasting food,” said lead study author Dr. Mireille Serlie, professor of endocrinology at Yale School of Medicine in New Haven, Connecticut.
The night before the testing, all 60 study participants had the same meal for dinner at home and did not eat again until the feeding tube was in place the next morning. As either sugars or fats entered the stomach via the tube, researchers used functional magnetic resonance imaging (fMRI) and single-photon emission computed tomography (SPECT) to capture the brain’s response over 30 minutes.
“The MRI shows where neurons in the brain are using oxygen in reaction to the nutrient — that part of the brain lights up,” Farooqi said. “The other scan measures dopamine, a hormone that is part of the reward system, which is a signal for finding something pleasurable, rewarding and motivating and then wanting that thing.”
Researchers were interested in how fats and glucose would individually trigger various areas of the brain connected to the rewarding aspects of food. They wanted to know if that would be different in people with obesity compared to those of normal weight.
“We were especially interested in the striatum, the part of the brain involved in the motivation to actually go and look for food and eat it,” Serlie said. Buried deep in the brain, the striatum also plays a role in emotion and habit formation.
In people with normal weight, the study found brain signals in the striatum slowed when either sugars or fats were put into the digestive system — evidence that the brain recognized the body had been fed.
“This overall reduction in brain activity makes sense because once food is in your stomach, you don’t need to go and get more food,” Serlie explained.
At the same time, levels of dopamine rose in those at normal weight, signaling that the reward centers of the brain were also activated.
Different findings for medically obese
However, when the same nutrients were given via feeding tube to people considered medically obese, brain activity did not slow, and dopamine levels did not rise.
This was especially true when the food was lipids or fats. That finding was interesting, Farooqi said, because the higher the fat content, the more rewarding the food: “That’s why you will genuinely want a burger instead of broccoli, the fat in the burger will biologically give a better response in the brain.”
Next, the study asked people with obesity to lose 10% of their body weight within three months — an amount of weight known to improve blood sugars, reset metabolism and boost overall health, Serlie said.
Tests were repeated as before — with surprising results. Losing weight did not reset the brain in people with obesity, Serlie said.
“Nothing changed — the brain still did not recognize fullness or feel satisfied,” she said. “Now, you might say three months is not long enough, or they didn’t lose enough weight.
“But this finding might also explain why people lose weight successfully and then regain all the weight a few years later — the impact on the brain may not be as reversible as we would like it to be.”
A 2018 meta-analysis of long-term weight loss clinical trials found 50% of a person’s original weight loss was regained after two years — by the fifth year, 80% of the weight was regained.
More research needed
Caution is needed in interpreting the findings, Serlie said, as much is unknown: “We don’t know when these profound changes in the brain happen during the course of weight gain. When does the brain start to slip and lose the sensing capacity?”
Obesity has a genetic component, and although the study attempted to control for that by excluding people with childhood onset obesity, it’s still possible that “genes are influencing our response in the brain to certain nutrients,” said Farooqi, who has studied the role of genes on weight for years.
Much more research is needed to fully understand what obesity does to the brain, and if that is triggered by the fat tissue itself, the types of food eaten, or other environmental and genetic factors.
“Are there changes that occurred in people as they gained weight? Or are there things that they were eating as they were gaining weight, such as ultra-processed foods, that caused a change in the brain? All of these are possible, and we don’t really know which it is,” Farooqi said.
Until science answers these questions, the study emphasizes, once again, that weight stigma has no place in the fight against obesity, Serlie said.
“The belief that weight gain can be solved simply by ‘just eating less, exercising more, and if you don’t do that, it’s a lack of willpower is so simplistic and so untrue,” she said.
“I think it’s important for people who are struggling with obesity to know that a malfunctioning brain may be the reason they wrestle with food intake,” Serlie said. “And hopefully this information will increase empathy for that struggle.”
注释：
reversibility: n
表示"可逆性；"，means "the quality of being reversible in either direction"，如：Because of the reversibility of methylation, the drugs reducing the level of methylation become a new way to cure leukemia. 由于甲基化的可逆性，降低甲基化水平的药物就成了治疗白血病的新手段。
rigorous: adj
表示" 严格的；严厉的；严峻的"，means " strict; "，如：The work failed to meet their rigorous standards. 工作没有达到他们的严格标准。He lived through the rigorous trials of revolutionary war.他经受了革命战争的严峻考验。He makes a rigorous study of the plant in the area.他对该地的植物进行了慎密的研究。
glucose: n
表示" 葡萄糖"，means "an important source of physiological energy"，如：We injected the glucose into the patient's vein.我们给病人的静脉里注射了葡萄糖。
resonance: n
表示" 共鸣"，means " quality of being resonant"，如：His voice can produce a great resonance. 他的声音能发出深沉的共鸣声。
photon: n
表示" 光子；光量子"，means "a quantum of electromagnetic radiation"，如：They are permanent as a photon is not. 它们是永恒的，而光子则不然。
tomography: n
表示"X线体层照相术"，means "(medicine) obtaining pictures of the interior of the body"，如：A chest computed tomography showed esophageal cancer with pneumopericardium. 其胸部电脑X线断层片也指出食道癌及心包膜腔积气。
dopamine： n
表示" 多巴胺(一种治脑神经病的药物)"，means "a monoamine neurotransmitter found in the brain and essential for the normal functioning of the central nervous system; as a drug (trade names Dopastat and Intropin) it is used to treat shock and hypotension"，如：Dopamine allows us to feel good when we laugh. 当我们笑的时候,多巴胺让我们感觉心情很好。
striatum: n
表示"终脑的皮层；中纹状体"，means "a striped mass of white and grey matter located in front of the thalamus in each cerebral hemisphere; consists of the caudate nucleus and the lenticular nucleus"，如：Experts believe that alcohol stimulates the striatum, an area of the brain that plays an important role in attraction. 专家们相信,酒精使大脑中纹状体兴奋,而这一区域对吸引力起重要作用。
stigma: n
表示"耻辱；污名"，means " mark of shame or disgrace"，如：There should be no stigma attached to being poor. 贫穷不应该与耻辱扯上任何关系。
simplistic: adj
表示" 过分简单化的"，means "characterized by extreme and often misleading simplicity"，如：It's a rather simplistic assessment of a complex situation. 这是对一复杂局面过于简单化的看法。
中文简要说明：
饱受肥胖困扰的人或许都有这样的经验：明明才刚吃完正餐没多久，却很快又感到饥饿，开始怀疑自己是否内分泌出了问题，而实际情况差不多就是如此。最近哈佛大学一项研究指出，肥胖者会表现出对食物欲求不满，正是因为肥胖破坏了大脑的感知能力，害大脑「生病了」。值得注意的是，这样的改变是不可逆的。这项研究刊登在国外知名期刊《自然新陈代谢》（Nature Metabolism）。
根据美国有线新闻网（CNN）报导，这项针对「肥胖」与大脑的认知功能的临床实验，由哈佛大学医学院教授阿波维恩（Caroline Apovian）主导。在实验的第一阶段，她找来30位医学定义上的肥胖者（BMI＞30），以及30位体重标准人士作为对照，让两组人马透过喂食管进食，半小时后，再以核磁共振造影及计算机断层监测受试者的脑部反应。
「我们想避开嘴巴（味觉），专注在肠道与大脑的关联，」研究团队成员之一、耶鲁大学医学院内分泌学教授塞利（Mireille Serlie）说。「我们对大脑的纹状体（striatum）特别感兴趣，这个部分驱动我们觅食的本能。」纹状体在情绪和习惯的形成上也扮演重要角色。
测试结果发现，体重正常者摄取食物后，纹状体的讯号会慢下来，意味着大脑认知到身体已经进食，不需要再寻找食物，同时体内负责传递快乐情绪的多巴胺（dopamine）则会上升。
相较之下，肥胖者即使进食后，脑内的纹状体仍持续处在活跃状态，多巴胺的指数也没有明显增加。
在第二阶段，研究人员要求30位肥胖者在3个月内减去10%体重——这样的减重幅度可以改善血糖、重启新陈代谢并促进健康，然后再重复第一阶段的实验。令人意外的是，即使成功减去体重后，他们的大脑并未因此「重置」，也就是说，即便摄取足够食物，大脑还是无法像一般人那样感到满足。
「（肥胖）对大脑造成影响，可逆性或许不如我们的期待，」塞利表示，而这也能解释为何许多人减肥成功后，往往不到几年又复胖。「认为减肥可以透过『少吃多动，减不下来是因为缺乏意志力』，这样的想法太过简单，也太不真实。」接下来专家将进一步研究大脑开始受损的时间点，以及损伤和食物种类之间的关联。
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