不只是胖：研究發現“脂肪來源”才是加速癌癥的關鍵

在肥胖問題日益嚴重的今天，科學界早已確認：肥胖會顯著提高患上至少13種主要癌癥的風險，包括乳腺癌、結腸癌和肝癌。

但近日發表于《Nature Metabolism》的一項十年研究提出了更具挑戰性的觀點：

導致癌癥加速的“罪魁禍首”，或許并不是脂肪總量，而是你吃進了什么樣的脂肪。

Obesity impairs the immune system’s ability to detect and destroy cancer cells. But researchers have long debated whether this is due to fat accumulation or fat type.

由普林斯頓大學Ludwig研究所的Lydia Lynch博士帶隊，并與哈佛大學Marcia Haigis教授合作，該研究得出明確結論：

“真正加速腫瘤發展的，是動物脂肪，而非單純的肥胖。”

盡管實驗小鼠體重一致，攝入動物脂肪（如豬油、黃油、牛脂）的肥胖小鼠，其抗腫瘤免疫系統功能顯著下降，腫瘤增長速度也更快。

而攝入植物脂肪（如椰子油、棕櫚油、橄欖油）的肥胖小鼠，免疫系統未見明顯抑制，甚至表現出更強的抗癌活性。

?? Mechanism：罪魁禍首是“代謝毒素”

團隊發現，動物脂肪在代謝過程中會產生大量長鏈酰基肉堿（long-chain acylcarnitines），這些物質：

• 破壞CTL和NK細胞的線粒體功能
  Disrupt mitochondrial activity in immune cells (CTLs & NK cells)

• 抑制關鍵免疫因子IFN-γ的產生
  Suppress the production of IFN-γ, essential for killing tumor cells

• 使免疫細胞“斷電”，無法殺死腫瘤細胞
  Cause metabolic shutdown of cancer-fighting cells

相比之下，棕櫚油飲食顯著激活免疫代謝調控因子c-Myc，使自然殺傷細胞保持活力，恢復抗癌功能。

“這項發現強調了飲食在維持免疫健康中的關鍵作用。更重要的是，這種脂肪來源的調整可能成為癌癥治療中的輔助策略。” — Dr. Lydia Lynch

中文要點

English Key Point

脂肪類型比脂肪數量更關鍵 Fat type matters more than fat quantity 動物脂肪削弱抗腫瘤免疫功能 Animal fats suppress tumor-fighting immune response 植物脂肪不但無害，甚至有益免疫功能 Plant fats preserve or enhance immune function 代謝毒素損傷線粒體，破壞CTL與NK細胞 Metabolites from animal fats damage mitochondria in immune cells 飲食結構應被納入癌癥治療策略中 Dietary fat should be considered in cancer therapy
你需要轉變的，可能不是體重，而是廚房里的那瓶油

如果你或你身邊的人正在經歷肥胖或癌癥治療，或許是時候思考：

不是少吃，而是換吃。

科學已經給出答案：吃“對”的脂肪，比一味減脂更關鍵。

原始英文研究內容（完整附錄）

Study finds animal-based fats fuel tumor growth in obese mice, plant fats do not
By Ludwig Institute for Cancer Research

Obesity elevates the risk of at least 13 major cancers, including those of the breast, colon, and liver. It also impairs immune responses that target tumors and are stimulated by cancer immunotherapies. But it has long been unclear whether these effects stem from the sheer adiposity—or mass of fat—in people living with obesity or from the specific dietary fats they consume.

Now, a decade-long study led by Ludwig Princeton's Lydia Lynch and reported in Nature Metabolism has provided a compelling answer to that question.

"Our study reveals that the source of dietary fat, not adiposity itself, is the primary factor that influences tumor growth in obese mice," said Lynch. "We found that high-fat diets derived from lard, beef tallow or butter compromise anti-tumor immunity and accelerate tumor growth in several tumor models of obese mice. Diets based on coconut oil, palm oil or olive oil, meanwhile, do not have this effect in equally obese mice. Our findings have implications for cancer prevention and care for people struggling with obesity."

Lynch and her colleagues—including Marcia Haigis, a senior author of the study and a member of the Ludwig Center at Harvard University—note that swapping out animal fats for plant fats might be a helpful dietary intervention for obese patients undergoing treatment for cancer. Such dietary changes could also potentially lower cancer risk for people living with obesity.

Lynch, Haigis and others have previously shown that obesity induces changes in the immune system and in the microenvironment of tumors that contribute to tumor progression. It does so by impairing the body's cancer surveillance system, undermining the ability of immune cells—namely cytotoxic T cells (CTLs) and natural killer (NK) cells—to infiltrate tumors and, once there, kill their cancerous quarry.

In the current study, Lynch and her colleagues took those findings a step further. They elucidate the mechanisms by which the metabolic derivatives of dietary animal fats impair NK cells and CTLs. They also show that it is this immune dysfunction that helps hasten tumor progression in obese mice—an effect not seen in obese mice fed plant-based fats. In fact, a palm oil-based diet even boosted anti-tumor immunity and slowed tumor growth in obese mice.

The researchers identified several metabolic intermediates of dietary fats, especially long-chain acylcarnitine species, that potently suppress NK cells and CTLs. These metabolites were especially elevated in obese mice reared on butter, lard, and beef tallow diets, but not in obese mice on plant-fat diets. They report that in CTLs, the molecules cause deep metabolic dysfunction in organelles known as mitochondria—the powerhouses of cells—compromising their cytotoxic function. This saps anti-tumor CTLs of their vitality, undermines their production of a factor (IFN-γ) critical to their function, and disables their cell-killing machinery.

The palm oil-based diet, on the other hand, prevented metabolic paralysis in the NK cells of obese mice, apparently by amplifying the activity of a master regulator of cellular metabolism known as c-Myc. The researchers found that Myc expression was reduced in mice fed animal fat—and also in NK cells from people living with obesity.

"These findings highlight the significance of diet in maintaining a healthy immune system," said Lynch. "More importantly, they indicate that modifications to fat in the diet may improve outcomes in obese people undergoing treatment for cancer and suggest such measures should be clinically evaluated as a potential dietary intervention for such patients."

英文關鍵詞

中文解釋

Obesity

肥胖，指體內脂肪過多影響健康的狀態

Tumor growth

腫瘤的生長過程

Immune responses

免疫系統對癌細胞的識別與反應

Cancer immunotherapies

通過免疫系統治療癌癥的方法

Adiposity

脂肪含量或脂肪堆積程度

Dietary fat

膳食中攝入的脂肪

Anti-tumor immunity

抵抗腫瘤的免疫能力

Lard

豬油

Beef tallow

牛脂

Butter

黃油

Coconut oil / Palm oil / Olive oil

椰子油 / 棕櫚油 / 橄欖油

Cancer prevention

癌癥預防措施

Cytotoxic T cells (CTLs)

細胞毒性T細胞

Natural killer (NK) cells

自然殺傷細胞

Tumor microenvironment

腫瘤所處的微觀環境

Immune dysfunction

免疫功能障礙

Metabolic derivatives

代謝產物

Long-chain acylcarnitines

長鏈酰基肉堿

Mitochondria

線粒體，細胞能量來源

Cytotoxic function

殺傷功能

IFN-γ (Interferon gamma)

干擾素γ，關鍵免疫因子

Cell-killing machinery

細胞的殺傷機制

Metabolic paralysis

免疫細胞代謝癱瘓

c-Myc

代謝調控關鍵蛋白

Master regulator

代謝主調控因子

Myc expression

c-Myc的表達水平

Dietary intervention

飲食干預手段

Metabolic dysfunction

代謝失調

Immune surveillance

免疫系統的癌細胞巡邏機制

Tumor progression

腫瘤進展，含擴散與轉移