跟著城市嚮導「老臺北胃」，用味道認識臺北

很多朋友來臺北，
都會問我同一個問題：
「臺北小吃那麼多，到底該從哪裡開始吃？」
夜市裡攤位一字排開、老店藏在巷弄轉角，
看起來都很有名，卻又怕吃錯、踩雷，
結果行程走完，反而沒真正記住臺北的味道。
我常被朋友笑說是「老臺北胃」。
不是因為特別會吃，而是因為在這座城市待久了，
知道哪些味道是陪著臺北人成長的日常。
這篇文章，就是我整理的一份清單。
如果你第一次來臺北，
我會帶你從這 10 樣最具代表性的臺北小吃開始，
不追一時爆紅、不走浮誇路線，
而是讓你吃完後能真正理解
原來，這就是臺灣的小吃文化。
跟著老臺北胃走，
用最簡單的方式，
把臺北的味道，一樣一樣記在心裡。

我怎麼選出這 10 大臺北小吃？

在臺北，
你隨便走進一條夜市或老街，
都可以輕易列出 30 種以上的小吃。
所以這份清單，
不是「臺北最好吃」的排名，
 而是我站在「第一次來臺北的旅客」角度，
做的推薦。
身為一個被朋友稱作「老臺北胃」的人，
我選這 10 樣小吃時，心裡一直放著幾個原則。

一吃就知道：這就是臺灣味

燒烤、火鍋很好吃，
但換個城市、換個國家，也吃得到。
我挑的，是那種
只要一入口，就會讓人聯想到的臺灣味。
 不需要解釋太多，舌頭就能懂。

不只是好吃，而是有「臺北日常感」

臺北的小吃迷人，
不只在味道，
而在它融入生活的方式。
我在意的是：

1. 會不會出現在早餐、宵夜、下班後
2. 有沒有陪伴這座城市很久的記憶

吃完之後，你會記得臺北

最後一個標準很簡單。
如果你回到家，
還會突然想起某個味道、某碗熱湯、某個攤位的香氣
那它就值得被放進這份清單裡。

接下來的 10 樣臺北小吃，
就是我會親自帶朋友去吃的在地美食。
不趕行程、不拚數量，
而是一口一口，
慢慢認識臺北。

第 1 家：饌堂－黑金滷肉飯（雙連店）｜一碗就懂臺灣人的日常

如果只能用一道料理，
 來解釋臺灣人的日常飲食，
 那我一定會先帶你吃滷肉飯。
在臺北，滷肉飯不是什麼特別的節慶料理，
 而是從早餐、午餐到宵夜，
 默默陪著很多人長大的味道。
而在眾多滷肉飯之中，
饌堂－黑金滷肉飯（雙連店），
 我很常帶第一次來臺北的朋友造訪的一家。

為什麼第一站，我會選饌堂？
饌堂的滷肉飯，走的是**「黑金系」路線**。
滷汁顏色深、香氣厚，
卻不死鹹、不油膩。
滷肉切得細緻，
肥肉入口即化，搭配熱騰騰的白飯，
每一口都是很完整、很臺灣的味道。
對第一次吃滷肉飯的旅客來說，
這種風味夠經典、也夠穩定，
不需要太多心理準備，就能理解為什麼臺灣人這麼愛它。

不只是好吃，而是「現在的臺北感」
饌堂並不是那種躲在深巷裡的老攤，
空間乾淨、節奏俐落，
卻沒有失去滷肉飯該有的靈魂。
這也是我會推薦給旅客的原因之一：
它保留了臺灣小吃的核心味道，
同時也讓第一次來臺北的人，
吃得安心、坐得舒服。

老臺北胃的帶路小提醒
如果是第一次來：

1. 一定要點招牌黑金滷肉飯
   
2. 可以加一顆滷蛋，風味會更完整
3. 搭配簡單的小菜，就很有臺灣家常感

這不是那種吃完會驚呼「哇！」的料理，
而是會讓你在幾口之後，
慢慢理解
原來，臺灣人的日常，就是這樣被一碗飯照顧著。

地址：103臺北市大同區雙連街55號1樓

電話：0225501379

菜單：https://bio.site/ZhuanTang

第 2 家：富宏牛肉麵｜臺北深夜也醒著的一碗熱湯

如果說滷肉飯代表的是臺灣人的日常，
 那牛肉麵，
 就是很多臺北人心中最有份量的一餐。
而在臺北提到牛肉麵，
 富宏牛肉麵，
 幾乎是夜貓族、加班族、外地旅客一定會被帶去的一站。

為什麼老臺北胃會帶你來吃富宏？
富宏最讓人印象深刻的，
不是華麗裝潢，
而是那鍋永遠冒著熱氣的紅燒湯頭。
湯色濃而不混，
帶著牛骨與醬香慢慢熬出的厚度，
喝起來溫潤、不刺激，
卻會在嘴裡留下很深的記憶點。
牛肉給得大方，
燉到軟嫩卻不鬆散，
搭配彈性十足的麵條，
每一口都很直接、很臺北。

不分時間，任何時候都適合的一碗麵
富宏牛肉麵最迷人的地方，
在於它陪伴了無數個臺北的夜晚。
不管是深夜下班、看完演唱會、
或是剛抵達臺北、還沒適應時差，
這裡總有一碗熱湯在等你。
對旅客來說，
這種不用算時間、不用擔心打烊的安心感，
本身就是一種臺北特色。

老臺北胃的帶路小提醒
第一次來富宏，我會這樣點：

1. 紅燒牛肉麵是首選
   
2. 如果想吃得更過癮，可以加點牛筋或牛肚
3. 湯先喝一口原味，再視情況調整辣度

這不是精緻料理，
卻是一碗能在任何時刻撐住你的牛肉麵。
在臺北，
很多夜晚，
就是靠這樣一碗熱湯走過來的。

地址：108臺北市萬華區洛陽街67號

電話：0223713028

菜單：https://www.facebook.com/pages/富宏牛肉麵-原建宏牛肉麵/

第 3 家：士林夜市・吉彖皮蛋涼麵｜臺北夏天最有記憶點的一口清爽

如果你在夏天來到臺北，
 一定會很快發現一件事
 這座城市，真的很熱。
也正因為這樣，
 臺北的小吃世界裡，
 才會出現像「涼麵」這樣的存在。
而在士林夜市，
 吉彖皮蛋涼麵，
 就是我很常帶旅客來吃的一家。

為什麼在夜市，我會帶你吃涼麵？
很多人對夜市的印象，
都是炸物、熱湯、重口味。
但真正的臺北夜市，
其實也很懂得照顧人的胃。
吉彖的涼麵，
冰涼的麵條拌上濃郁芝麻醬，
再加上切得細緻的皮蛋，
入口的第一瞬間，
就是一種「被降溫」的感覺。
那種清爽，
不是沒味道，
而是在濃香與清涼之間取得剛剛好的平衡。

皮蛋，是靈魂，也是臺灣味的關鍵
對很多外國旅客來說，
皮蛋是既好奇、又有點猶豫的存在。
但我常說，
如果要嘗試皮蛋，
涼麵是一個非常溫柔的起點。
芝麻醬的香氣會先接住味蕾，
皮蛋的風味則在後段慢慢出現，
不衝、不嗆，
反而多了一層深度。
很多人吃完後，
都會露出那種「原來是這樣啊」的表情。

老臺北胃的帶路小提醒
第一次點吉彖皮蛋涼麵，我會建議：

1. 一定要選皮蛋款，才吃得到特色
2. 醬料先拌勻，再吃，風味會更完整
3. 如果天氣真的很熱，這一碗會救你一整晚

這不是華麗的小吃，
卻非常臺北。
在悶熱的夜晚，
站在夜市人潮裡，
吃著一碗涼麵，
你會突然明白——

原來臺北的小吃，連氣候都一起考慮進去了。

地址：111臺北市士林區基河路114號

電話：0981014155

菜單：https://www.facebook.com/profile.php?id=100064238763064

第 4 家：胖老闆誠意肉粥｜臺北人深夜最踏實的一碗粥

如果你問我，
 臺北人在深夜、下班後，
 最容易感到被安慰的食物是什麼——
 我會毫不猶豫地說：肉粥。
而提到肉粥，
 胖老闆誠意肉粥，
 就是很多老臺北人口中的那一味。

為什麼這一碗粥，會被叫做「誠意」？
胖老闆的肉粥，看起來很簡單。
白粥、肉燥、配菜，
沒有華麗擺盤，也沒有複雜作法。
但真正坐下來吃，你會發現：
這碗粥，不敷衍任何一個細節。
粥體滑順、不稀薄，
肉燥香而不膩，
搭配各式家常小菜，
一口一口吃下去，
很自然就會放慢速度。
這種味道，
不是要你驚艷，
而是要你安心。

這不是觀光小吃，而是臺北人的生活片段
胖老闆誠意肉粥，
最迷人的地方，
就是它的客人。
你會看到：

1. 剛下班的上班族
2. 熬夜後來吃一碗熱粥的人
3. 熟門熟路、點菜不用看菜單的老客人

這些畫面，
比任何裝潢都更能說明這家店在臺北的位置。
對旅客來說，
這是一個走進臺北人日常的入口。

老臺北胃的帶路小提醒
第一次來吃，我會這樣建議：

1. 肉粥一定要點，這是主角
2. 配幾樣小菜一起吃，才有完整體驗
3. 不用急，慢慢吃，這碗粥就是要你放鬆

這不是為了拍照而存在的小吃，
而是那種
**會讓人記得「那天晚上，我在臺北吃了一碗很溫暖的粥」**的味道。

地址：10491臺北市中山區長春路89-3號

電話：0913806139

菜單：https://lin.ee/xxbYZyS

第 5 家：圓環邊蚵仔煎｜夜市裡最不能缺席的臺灣經典

如果要選一道
 最常出現在旅客記憶裡的臺灣小吃，
 蚵仔煎一定排得上前幾名。
而在臺北，
 圓環邊蚵仔煎，
 就是那種很多臺北人從小吃到大的存在。

為什麼蚵仔煎，這麼能代表臺灣？
蚵仔煎的魅力，
不在於精緻，
而在於它把幾種看似簡單的食材，
煎成了一種獨特的口感。
新鮮蚵仔的海味、
雞蛋的香氣、
地瓜粉形成的滑嫩外皮，
最後再淋上甜中帶鹹的醬汁，
一口下去，
就是夜市的完整畫面。
這種味道，
很難在其他國家找到替代品。

圓環邊，吃的是記憶感
圓環邊蚵仔煎，
沒有多餘的包裝，
也不刻意迎合潮流。
它留下來的原因很簡單
味道夠穩、節奏夠快、
讓人一吃就知道「對，就是這個」。
對旅客來說，
這是一家
不需要研究、不需要比較，就能安心點蚵仔煎的地方。

老臺北胃的帶路小提醒
第一次吃蚵仔煎，我會這樣建議：

1. 趁熱吃，口感最好
   
2. 不用急著加辣，先吃原味
3. 醬汁是靈魂，別急著把它拌掉

蚵仔煎不是細嚼慢嚥的料理，
它屬於人聲鼎沸、鍋鏟作響的夜市時刻。
站在人群裡，
吃著一盤熱騰騰的蚵仔煎，
你會很清楚地感受到
這，就是臺北的夜晚。

地址：103臺北市大同區寧夏路46號

電話：0225580198

菜單：https://oystera.com.tw/menu

第 6 家：阿淑清蒸肉圓｜第一次吃肉圓，就該從這裡開始

說到臺灣小吃，
 很多人腦中一定會出現「肉圓」兩個字。
但真正吃過之後才會發現，
 肉圓，從來不只有一種樣子。
在臺北，
 阿淑清蒸肉圓，
 就是我很常拿來介紹「清蒸派肉圓」的一家。

清蒸肉圓，和你想像的不一樣
不少旅客對肉圓的第一印象，
來自油炸版本，
外皮厚、口感重。
而阿淑的清蒸肉圓，
完全是另一個方向。
外皮晶瑩、滑嫩，
帶著自然的彈性，
不油、不膩，
一入口反而顯得清爽。
內餡扎實，
豬肉香氣清楚，
搭配特製醬汁，
味道層次簡單卻很乾淨。

為什麼我會推薦給第一次來臺北的旅客？
因為這顆肉圓，
不需要適應期。
它不刺激、不厚重，
即使是第一次嘗試臺灣小吃的人，
也能輕鬆接受。
對旅客來說，
這是一顆
「吃得懂、也記得住」的肉圓。

老臺北胃的帶路小提醒
第一次來阿淑，我會這樣吃：

1. 直接點一顆清蒸肉圓，吃原味
2. 醬汁先別全部拌開，邊吃邊調整
3. 放慢速度，感受外皮的口感變化

這不是夜市裡熱鬧喧囂的料理，
而是那種
安靜地展現臺灣小吃功夫的味道。
當你吃完這顆肉圓，
會更明白一件事
臺灣小吃的魅力，
往往藏在這些細節裡。

地址：242新北市新莊區復興路一段141號

電話：0229975505

第 7 家：胡記米粉湯｜一碗最貼近臺北早晨的味道

如果說前面幾樣小吃，
 是臺北的熱鬧與記憶，
 那麼米粉湯，
 就是這座城市最真實的日常。
而在臺北，
 胡記米粉湯，
 是很多人從小吃到大的存在。

為什麼米粉湯，這麼「臺北」？
米粉湯不是重口味料理，
它靠的不是刺激，
而是一碗清澈卻有深度的湯。
胡記的湯頭，
用豬骨慢慢熬出香氣，
喝起來清爽、不油，
卻能在喉嚨留下溫度。
米粉細軟，
吸附湯汁後入口順滑，
簡單到不能再簡單，
卻正是臺北人習以為常的早晨風景。

配菜，才是這一碗的靈魂延伸
在胡記吃米粉湯，
主角雖然是湯，
但真正讓人滿足的，
往往是那些小菜。
紅燒肉、豬內臟、燙青菜，
隨意點上幾樣，
湯一口、菜一口，
就是很多臺北人記憶中的早餐組合。
對旅客來說，
這是一種
不需要解釋，就能融入的臺北生活感。

老臺北胃的帶路小提醒
第一次來胡記，我會這樣建議：

1. 一定要點米粉湯，湯先喝
2. 再配 1～2 樣小菜，體驗會完整很多
3. 這一餐適合慢慢吃，不用趕

這不是為了觀光而存在的小吃，
而是一碗
每天準時出現在臺北人生活裡的湯。
當你坐在店裡，
聽著湯勺碰撞的聲音，
你會突然感覺到——
原來，臺北的早晨，
就是從這樣一碗米粉湯開始的。

地址：106臺北市大安區大安路一段9號1樓

電話：0227212120

第 8 家：藍家割包｜一口咬下的臺灣街頭記憶

如果要選一道
 外國旅客一看到就會好奇、吃完又會記住的小吃，
 割包，一定在名單裡。
而在臺北，
 藍家割包，
 就是我很放心帶旅客來認識這道經典的一站。

割包，為什麼被叫做「臺灣漢堡」？
割包的結構其實很簡單：
鬆軟的白饅頭、
燉得入味的滷五花肉、
酸菜、花生粉、香菜。
但真正迷人的，
是這些元素組合在一起時，
形成的層次感。
肉香、甜味、鹹味、清爽度，
在一口之間同時出現，
沒有誰搶戲，
卻彼此剛好。
這種平衡感，
正是臺灣小吃很迷人的地方。

藍家割包不是走浮誇路線，
它給人的感覺很直接
就是你期待中的割包樣子。
饅頭柔軟不乾，
五花肉肥瘦比例恰到好處，
入口即化卻不膩口，
花生粉的甜香收尾，
讓整體味道非常完整。
對第一次吃割包的旅客來說，
這是一個
不會出錯、也很容易愛上的版本。

老臺北胃的帶路小提醒
第一次吃藍家割包，我會這樣建議：

1. 直接點招牌割包，不要改配料
2. 如果有香菜，建議保留，味道會更完整
3. 趁熱吃，饅頭口感最好

割包不是精緻料理，
卻非常有記憶點。
站在街頭，
拿著一顆熱騰騰的割包，
邊走邊吃，
你會很清楚地感受到
這一口，就是臺灣的街頭生活。

地址：100臺北市中正區羅斯福路三段316巷8弄3號

電話：0223682060

菜單：https://instagram.com/lan_jia_gua_bao?utm_medium=copy_link

第 9 家：御品元冰火湯圓｜臺北夜晚最溫柔的一碗甜

吃了一整天的臺北小吃，
 到了這個時候，
 胃其實已經差不多滿了。
但只要天氣一涼，
 或夜色慢慢降下來，
 你還是會想找一碗——
 不是為了吃飽，而是為了舒服的甜點。
這時候，我通常會帶你來 御品元冰火湯圓。

為什麼叫「冰火」？這碗湯圓的關鍵就在這裡
御品元最有特色的地方，
就在於它的「冰火交錯」。
熱騰騰的湯圓，
外皮軟糯、內餡濃香，
搭配冰涼清甜的桂花蜜湯，
一口下去，
溫度在嘴裡交替出現。
不是衝突，
而是一種很細膩的平衡。
這樣的吃法，
也正是臺灣甜點很擅長的地方——
不張揚，但很有記憶點。

這是一碗，會讓人慢下來的甜點
和夜市裡熱鬧的甜品不同，
御品元的冰火湯圓，
更像是一個讓人停下腳步的存在。
你會發現，
坐在這裡吃湯圓的人，
說話聲都會不自覺地變小。
對旅客來說，
這不只是吃甜點，
而是一個
把白天的熱鬧慢慢收進回憶裡的時刻。

老臺北胃的帶路小提醒
第一次吃御品元，我會這樣建議：

1. 點招牌冰火湯圓，體驗完整特色
2. 先單吃湯圓，再搭配湯一起吃
3. 放慢速度，這一碗不適合趕時間

這不是為了拍照而存在的甜點，
而是一碗
會讓你記得「那天晚上在臺北，很舒服」的湯圓。

地址：106臺北市大安區通化街39巷50弄31號

電話：0955861816

菜單：https://instagram.com/lan_jia_gua_bao

第 10 家：頃刻間綠豆沙牛奶專賣店｜把臺北的味道，留在最後一口清甜

走到這一站，
 其實已經不需要再吃什麼大份量的東西了。
這時候，
 最適合的，
 是一杯不吵鬧、不張揚，
 卻會默默留在記憶裡的飲品。
頃刻間綠豆沙牛奶，
 就是我很常用來替一天畫下句點的選擇。

綠豆沙牛奶，為什麼這麼「臺灣」？
在臺灣，
飲料不只是解渴，
而是一種生活節奏。
綠豆沙牛奶看起來簡單，
但真正好喝的版本，
靠的是火候、比例，
還有耐心。
頃刻間的綠豆沙，
口感細緻、不粗顆，
甜度自然、不膩口，
牛奶的加入，
讓整杯變得柔順而溫和。
這不是衝擊味蕾的飲料，
而是一種
喝完之後，會覺得剛剛那一刻很舒服的甜。

為什麼我會用它當作最後一站？
因為它很臺北。
你可以外帶，
邊走邊喝；
也可以站在店門口，
慢慢把杯子喝空。
沒有儀式感，
卻很真實。
對旅客來說，
這杯綠豆沙牛奶，
就像是把今天吃過的所有味道，
溫柔地整理好，
帶走。

老臺北胃的帶路小提醒
第一次喝頃刻間，我會這樣建議：

1. 直接點招牌綠豆沙牛奶
   
2. 正常甜就很剛好，不用特別調整
3. 找個角落慢慢喝，別急著趕路

這一杯，
不會讓你驚呼，
卻會在回程的路上，
突然想起來。
原來，臺北的味道，是這樣結束一天的。

地址：111臺北市士林區小北街1號

電話：0228818619

菜單：https://instagram.com/chill_out_moment?igshid=YmMyMTA2M2Y=

如果只有 3 天的自助旅行在臺北，怎麼吃這 10 家？

第一次來臺北，
時間有限、胃容量也有限，
與其每一家都趕，不如照著節奏吃。
這份 3 天小吃路線，
是老臺北胃會帶朋友實際走的版本：
不爆走、不硬塞，
讓你每天都吃得剛剛好。

臺北 3 天小吃推薦行程表（老臺北胃版本）

天數	時段	店家名稱	小吃類型
Day 1	午餐	饌堂－黑金滷肉飯（雙連店）	滷肉飯
Day 1	下午	阿淑清蒸肉圓	肉圓
Day 1	晚餐	富宏牛肉麵	牛肉麵
Day 1	宵夜	胖老闆誠意肉粥	粥品
Day 2	早餐	胡記米粉湯	米粉湯
Day 2	下午	藍家割包	割包
Day 2	晚上	士林夜市－吉彖皮蛋涼麵	涼麵
Day 2	夜市	圓環邊蚵仔煎	蚵仔煎
Day 3	下午	御品元冰火湯圓	甜點
Day 3	收尾	頃刻間綠豆沙牛奶專賣店	飲品

雖然每個小吃的地點都有一點距離，但是你也知道，好吃的小吃，是值得你花一點時間前往品嘗
老臺北胃的小提醒

1. 不需要每一家都點到最滿
2. 留一點餘裕，才會想再回來
3. 臺北小吃的魅力，不在於吃多少，而在於記住了什麼味道
   

當你照著這 3 天走完，
你會發現，
臺北不是靠一兩道名菜被記住的，
而是靠這些看似日常、卻很真實的小吃。
下次再來，老臺北胃再帶你吃更深的那一輪。

老臺北胃帶路｜這 10 口，就是我心中的臺北

寫到這裡，
 其實已經不是在推薦哪一家小吃了。
而是在回頭看，
 這座城市，是怎麼用食物陪著人生活的。
滷肉飯、牛肉麵、肉粥、米粉湯，
 不是為了成為觀光名單而存在，
 而是每天默默出現在臺北人的日子裡。
夜市裡的蚵仔煎、涼麵、割包，
 熱鬧、吵雜、節奏很快，
 卻也正是臺北最真實的樣子。
而最後那碗湯圓、那杯綠豆沙牛奶，
 則是在一天結束時，
 替味蕾留下一個溫柔的句點。

如果你問我，
「這 10 家是不是臺北最好吃的小吃？」
我會說，
它們不一定是排行榜第一名，
卻是我真的會帶朋友去吃的版本。
因為它們吃得到：

1. 臺北人的日常
2. 巷弄裡的熟悉感
3. 不需要解釋，就能被理解的味道

如果你是第一次來臺北，
跟著這份清單走，
你不一定會吃得最飽，
但你一定會記得——
臺北，是什麼味道。
而如果有一天，
你又再回到這座城市，
走進熟悉的街口、
看到冒著熱氣的小攤，
你也會開始懂得，
為什麼老臺北胃，
總是記得這些看似平凡的滋味。
因為，真正留在心裡的，
從來不是吃過多少，
而是哪一口，讓你想起臺北。

饌堂－黑金滷肉飯（雙連店）年輕人會喜歡嗎？

走完這 10 家，

你可能會發現一件事圓環邊蚵仔煎推薦點什麼？

臺北的小吃，其實不急著被你記住。

它們就安靜地存在在街角、夜市、轉彎處，御品元冰火湯圓口味會太重嗎？

等你有一天，再回到這座城市。胖老闆誠意肉粥吃過會回訪嗎？

如果你是第一次來臺北，士林夜市－吉彖皮蛋涼麵值得專程去嗎？

希望這份「老臺北胃帶路」的清單，

能幫你少一點猶豫、多一點安心。

不用擔心踩雷，胡記米粉湯當正餐適合嗎？

也不用為了排行而奔波，胡記米粉湯本地人會吃嗎？

只要照著節奏走，

你就會吃到屬於自己的臺北味道。

而如果你已經來過臺北，

那更希望這篇文章，胡記米粉湯新手友善嗎？

能帶你走進那些

你可能錯過、卻一直都在的日常小吃。

因為真正迷人的旅行，

從來不是把清單全部打勾，

而是某一天，

你突然想起那碗飯、那口湯、那杯甜，胖老闆誠意肉粥當正餐適合嗎？

然後在心裡對自己說一句：頃刻間綠豆沙牛奶專賣店會不會太油？

「下次再去臺北，還想再吃一次。」

把這篇文章存起來、分享給一起旅行的人，

或是在規劃行程時，再回來看看。

讓味道，成為你認識臺北的方式。

下一次來臺北，

別急著走遠。

老臺北胃，藍家割包口味會太清淡嗎？

會一直在這些地方，

等你再回來。

The human body doesn’t produce vitamin B1, so we must obtain it from our food. On its way from the gut to the cells throughout the body, vitamin B1 must cross several cell membranes. One of the most critical hurdles for B1 is the blood-brain barrier. EMBL Hamburg’s Löw Group has provided detailed molecular insights into how vitamin B1 overcomes these obstacles. Credit: Isabel Romero Calvo/EMBL Scientists from EMBL Hamburg and CSSB have uncovered the molecular mechanisms behind how the body absorbs vitamin B1, potentially leading to strategies to prevent hidden, dangerous B1 deficiencies in patients. Vitamin B1, or thiamine, is vital for cell survival, yet the human body cannot produce it. To maintain healthy levels, it’s important to consume foods such as salmon, legumes, and brown rice. Ensuring adequate intake is essential, as a B1 deficiency can lead to severe cardiovascular and nervous system dysfunctions, disability, and even death. However, sometimes, B1 deficiency may develop in the brain and other vital organs as a side effect of some drugs. This can happen despite normal B1 levels in the blood, which often makes such deficiencies go undetected before it’s too late. To understand what’s behind such hidden deficiencies, the Löw Group at EMBL Hamburg and CSSB and collaborators at VIB-VUB Center for Structural Biology used structural biology and biophysical techniques to investigate how vitamin B1 travels in our body to reach different tissues, and what factors can hinder its progress. Vitamin B1’s hurdle run On its journey from the gut to the body’s cells, vitamin B1 must pass through several membranes, which act as barriers – starting with the gut wall, then blood vessels, organs, and finally, the membranes of individual cells. The most stringent of these is the blood-brain barrier, which seals the brain off from toxins that might enter from the bloodstream. However, the barrier also makes it difficult for essential nutrients, including vitamins, to cross. To allow vitamins and other nutrients to reach cells throughout the body, these membranes are equipped with specialized transporter molecules that let them pass. In vitamin B1’s case, this job is done mostly by two transporters: SLC19A2 and SLC19A3. While we know these transporters are important for human health, it has been unclear how exactly they work on the molecular level. To uncover this, the Löw Group investigated SLC19A3, the transporter essential for getting B1 across the gut wall and the blood-brain barrier – two crucial steps in the vitamin’s journey. To observe the transporter in action, they created a ‘molecular movie’ by putting together a series of snapshots obtained with cryo-electron microscopy (cryo-EM). “With this, we could capture the dynamics of the transport process and visualize molecular details of how the transporter recognizes and pushes the B1 molecule across the cell membrane,” said Christian Löw, Group Leader and corresponding author of the study. Insights into rare diseases The molecular snapshots enabled the scientists to determine which parts of the SLC19A3 transporter are the most critical for it to work correctly. If these parts malfunction, the transporter won’t work. This explains why mutations in these critical parts impair B1 transport to the brain and lead to severe neurological symptoms. These rare conditions, which start manifesting symptoms in infancy, are treated with high doses of B1 and other compounds. Despite this, one in 20 patients die and nearly one-third still suffer from symptoms. To investigate this, the scientists created a version of the SLC19A3 transporter carrying a mutation that causes a severe brain disease called BTBGD. This lets them observe exactly how the mutation affects the transporter’s molecular structure and makes it unreceptive to B1. Understanding this disease-causing mechanism might help to design more effective treatments for BTBGD in the future. Drugs that can cause hidden B1 deficiencies Severe B1 deficiency symptoms can be caused not only by rare mutations, but also by some medications. Several commonly prescribed drugs, including some antidepressants, antibiotics, and oncological medications, impair SLC19A3. This can potentially lead to dangerous B1 deficiencies throughout the body or in specific organs or tissues. Brain-specific deficiencies are especially dangerous because they can occur even when our blood levels of B1 are normal, making them undetectable by standard blood tests. This hidden deficiency can quietly lead to serious, potentially fatal brain dysfunction. “While medicine already knows a few drugs that have the potential to cause hidden B1 deficiencies, there may be many more that we’re unaware of,” said Florian Gabriel, PhD student at EMBL Hamburg and the first author of the study. “Identifying them isn’t straightforward, so our research aimed to make it easier. We’ve uncovered the molecular basis of how drug molecules block the SLC19A3 transporter and we are currently using that knowledge to screen all FDA- and EMA-approved drugs for similar effects.” The Löw Group also identified the structural features that make a drug likely to impair B1 transport. To do this, they used cryo-EM and biophysical techniques to analyze how known blockers interact with SLC19A3. Using this knowledge, they have identified seven new drugs that block the B1 transporter in vitro and are likely to do it in the human body as well. These include several antidepressants, the antiparasitic hydroxychloroquine, and three cancer drugs. While these findings still need to be confirmed in humans, they are a first step to protecting patients from potentially dangerous drug-induced B1 deficiencies in the future. “These results will not only help to better monitor the health of patients taking those drugs, but might also help to design new drugs in the future that won’t have this side effect,” said Löw. “We believe our work could also create a basis for studying how medicines interact with similar transporters in the human body. In the long term, it might also guide the design of future drugs that could use those transporters to reach target organs more efficiently.” Reference: “Structural basis of thiamine transport and drug recognition by SLC19A3” by Florian Gabriel, Lea Spriestersbach, Antonia Fuhrmann, Katharina E. J. Jungnickel, Siavash Mostafavi, Els Pardon, Jan Steyaert and Christian Löw, 2 October 2024, Nature Communications. DOI: 10.1038/s41467-024-52872-8 Funding: UHH, Deutsche Forschungsgemeinschaft, Boehringer Ingelheim, Nanobodies4Instruct, Instruct-ERIC, EMBO

A comprehensive study by MoTrPAC has revealed that exercise induces widespread molecular changes across all studied organs in rats, suggesting complex biological processes that could inform personalized exercise regimens and treatments for conditions like non-alcoholic fatty liver disease. Credit: SciTechDaily.com Prolonged physical activity in rats results in profound changes to RNA, proteins, and metabolites in nearly all tissues, providing clues to many human health conditions. The health benefits of exercise are well known but new research shows that the body’s response to exercise is more complex and far-reaching than previously thought. In a study on rats, a team of scientists from across the United States found that physical activity causes many cellular and molecular changes in all 19 of the organs they studied in the animals. Exercise lowers the risk of many diseases, but scientists still don’t fully understand how exercise changes the body on a molecular level. Most studies have focused on a single organ, sex, or time point, and only include one or two data types. Comprehensive Molecular Analysis To take a more comprehensive look at the biology of exercise, scientists with the Molecular Transducers of Physical Activity Consortium (MoTrPAC) used an array of techniques in the lab to analyze molecular changes in rats as they were put through the paces of weeks of intense exercise. Their findings were published on May 1 in the journal Nature. The team studied a range of tissues from the animals, such as the heart, brain, and lungs. They found that each of the organs they looked at changed with exercise, helping the body to regulate the immune system, respond to stress, and control pathways connected to inflammatory liver disease, heart disease, and tissue injury. Potential Health Implications The data provide potential clues into many different human health conditions; for example, the researchers found a possible explanation for why the liver becomes less fatty during exercise, which could help in the development of new treatments for non-alcoholic fatty liver disease. The team hopes that their findings could one day be used to tailor exercise to an individual’s health status or to develop treatments that mimic the effects of physical activity for people who are unable to exercise. They have already started studies on people to track the molecular effects of exercise. Broader Research Collaboration Launched in 2016, MoTrPAC draws together scientists from the Broad Institute of MIT and Harvard, Stanford University, the National Institutes of Health, and other institutions to shed light on the biological processes that underlie the health benefits of exercise. The Broad project was originally conceived of by Steve Carr, senior director of Broad’s Proteomics Platform; Clary Clish, senior director of Broad’s Metabolomics Platform; Robert Gerszten, a senior associate member at the Broad and chief of cardiovascular medicine at Beth Israel Deaconess Medical Center; and Christopher Newgard, a professor of nutrition at Duke University. Co-first authors on the study include Pierre Jean-Beltran, a postdoctoral researcher in Carr’s group at Broad when the study began, as well as David Amar and Nicole Gay of Stanford. Courtney Dennis and Julian Avila, both researchers in Clish’s group, were also co-authors on the manuscript. “It took a village of scientists with distinct scientific backgrounds to generate and integrate the massive amount of high quality data produced,” said Carr, a co-senior author of the study. “This is the first whole-organism map looking at the effects of training in multiple different organs. The resource produced will be enormously valuable, and has already produced many potentially novel biological insights for further exploration.” The team has made all of the animal data available in an online public repository. Other scientists can use this site to download, for example, information about the proteins changing in abundance in the lungs of female rats after eight weeks of regular exercise on a treadmill, or the RNA response to exercise in all organs of male and female rats over time. Whole-Body Analysis Conducting such a large and detailed study required a lot of planning. “The amount of coordination that all of the labs involved in this study had to do was phenomenal,” said Clish. In partnership with Sue Bodine at the Carver College of Medicine at the University of Iowa, whose group collected tissue samples from animals after up to eight weeks of training, other members of the MoTrPAC team divided the samples up so that each lab — Carr’s team analyzing proteins, Clish’s studying metabolites, and others — would examine virtually identical samples. “A lot of large-scale studies only focus on one or two data types,” said Natalie Clark, a computational scientist in Carr’s group. “But here we have a breadth of many different experiments on the same tissues, and that’s given us a global overview of how all of these different molecular layers contribute to exercise response.” In all, the teams performed nearly 10,000 assays to make about 15 million measurements on blood and 18 solid tissues. They found that exercise impacted thousands of molecules, with the most extreme changes in the adrenal gland, which produces hormones that regulate many important processes such as immunity, metabolism, and blood pressure. The researchers uncovered sex differences in several organs, particularly related to the immune response over time. Most immune-signaling molecules unique to females showed changes in levels between one and two weeks of training, whereas those in males showed differences between four and eight weeks. Some responses were consistent across sexes and organs. For example, the researchers found that heat-shock proteins, which are produced by cells in response to stress, were regulated in the same ways across different tissues. But other insights were tissue-specific. To their surprise, Carr’s team found an increase in acetylation of mitochondrial proteins involved in energy production, and in a phosphorylation signal that regulates energy storage, both in the liver that changed during exercise. These changes could help the liver become less fatty and less prone to disease with exercise, and could give researchers a target for future treatments of non-alcoholic fatty liver disease. Novel Biological Insights “Even though the liver is not directly involved in exercise, it still undergoes changes that could improve health. No one speculated that we’d see these acetylation and phosphorylation changes in the liver after exercise training,” said Jean-Beltran. “This highlights why we deploy all of these different molecular modalities — exercise is a very complex process, and this is just the tip of the iceberg.” “Two or three generations of research associates matured on this consortium project and learned what it means to carefully design a study and process samples,” added Hasmik Keshishian, a senior group leader in Carr’s group and co-author of the study. “Now we are seeing the results of our work: biologically insightful findings that are yielding from the high quality data we and others have generated. That’s really fulfilling.” Other MoTrPAC papers published on May 1 include deeper dives into the response of fat and mitochondria in different tissues to exercise. Additional MoTrPAC studies are underway to study the effects of exercise on young adult and older rats, and the short-term effects of 30-minute bouts of physical activity. The consortium has also begun human studies, and are recruiting about 1,500 individuals of diverse ages, sexes, ancestries, and activity levels for a clinical trial to study the effects of both endurance and resistance exercise in children and adults. For more on this research, see Scientists Decode the Molecular Impact of Exercise. Reference: “Temporal dynamics of the multi-omic response to endurance exercise training” by MoTrPAC Study Group, Lead Analysts and MoTrPAC Study Group, 1 May 2024, Nature. DOI: 10.1038/s41586-023-06877-w This work was supported by the National Institutes of Health.

Octopuses are mollusks, a large evolutionary group to which slugs and snails also belong. Their complex brains, and those of other closely-related cephalopods, like squid and cuttlefish, have evolved separately from vertebrates, and so octopuses are often referred to as alien-like. Here, a day octopus (Octopus cyanea) poses with a Shisa, a creature from Okinawan folklore. Credit: Michael Kuba Scientists have figured out how to capture brain activity in octopuses that are awake and moving – a breakthrough step in understanding how the brain controls their behavior. By implanting electrodes and a data logger directly into the creatures, scientists have achieved the remarkable accomplishment of recording brain activity from octopuses while they move around freely. Published online in the journal Current Biology on February 23, the study represents a critical step forward in figuring out how octopus brains control their behavior, and could provide clues to the common principles needed for intelligence and cognition to occur. “If we want to understand how the brain works, octopuses are the perfect animal to study as a comparison to mammals. They have a large brain, an amazingly unique body, and advanced cognitive abilities that have developed completely differently from those of vertebrates,” said Dr. Tamar Gutnick, first author and former postdoctoral researcher in the Physics and Biology Unit at the Okinawa Institute of Science and Technology (OIST). The researchers recorded the brain activity of an octopus for 12 hours. Here, the octopus is in active sleep, a stage in which there are rapid changes in color and texture, as well as fast sucker motion. Credit: Current Biology But measuring the brainwaves of octopuses has proven a real technical challenge. Unlike vertebrates, octopuses are soft-bodied, so they have no skull to anchor the recording equipment onto, to prevent it from being removed. “Octopuses have eight powerful and ultra-flexible arms, which can reach absolutely anywhere on their body,” said Dr. Gutnick. “If we tried to attach wires to them, they would immediately rip if off, so we needed a way of getting the equipment completely out of their reach, by placing it under their skin.” The researchers settled on small and lightweight data loggers as the solution, which were originally designed to track the brain activity of birds during flight. The team adapted the devices to make them waterproof, but still small enough to easily fit inside the octopuses. The batteries, which needed to work in a low-air environment, allowed up to 12 hours of continuous recording. The day octopus, Octopus cyanea, camouflages itself against the coral reef. Credit: Keishu Asada The researchers chose Octopus cyanea, more commonly known as the day octopus, as their model animal, due to its larger size. They anesthetized three octopuses and implanted a logger into a cavity in the muscle wall of the mantle. The scientists then implanted the electrodes into an area of the octopus’ brain called the vertical lobe and median superior frontal lobe, which is the most accessible area. This brain region is also believed to be important for visual learning and memory, which are brain processes that Dr. Gutnick is particularly interested in understanding. First Observations of Octopus Brain Activity Once the surgery was complete, the octopuses were returned to their home tank and monitored by video. After five minutes, the octopuses had recovered and spent the following 12 hours sleeping, eating and moving around their tank, as their brain activity was recorded. The logger and electrodes were then removed from the octopuses, and the data was synchronized to the video. The researchers identified several distinct patterns of brain activity, some of which were similar in size and shape to those seen in mammals, whilst others were very long-lasting, slow oscillations that have not been described before. The researchers were not yet able to link these brain activity patterns to specific behaviors from the videos. However, this is not completely surprising, Dr. Gutnick explained, as they didn’t require the animals to do specific learning tasks. “This is an area that’s associated with learning and memory, so in order to explore this circuit, we really need to do repetitive, memory tasks with the octopuses. That’s something we’re hoping to do very soon!” The researchers also believe that this method of recording brain activity from freely moving octopuses can be used in other octopus species and could help solve questions in many other areas of octopus cognition, including how they learn, socialize, and control the movement of their body and arms. “This is a really pivotal study, but it’s just the first step,” said Prof. Michael Kuba, who led the project at the OIST Physics and Biology Unit and now continues at the University of Naples Federico II. “Octopus are so clever, but right now, we know so little about how their brains work. This technique means we now have the ability to peer into their brain while they are doing specific tasks. That’s really exciting and powerful.” Reference: “Recording Electrical Activity from the Brain of Behaving Octopus” by Tamar Gutnick, Andreas Neef, Andrii Cherninskyi, Fabienne Ziadi-Kunzli, Anna Di Cosmo, Hans-Peter Lipp and Michael Kuba, 23 February 2023, Current Biology. DOI: 10.2139/ssrn.4309084 The study involved an international collaboration between researchers in Japan, Italy, Germany, Ukraine, and Switzerland.

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