"Nature": The reason for the calorie restriction diet to kill cancer cells has been found!

To treat diseases, medicine alone is not enough.
Taking appropriate diet and exercise methods can also produce 1+1>2 effects
.

For example, diets that restrict calorie intake and can cause fasting-like metabolic changes in the body (simulating fasting diets), as well as high-fat, low-carbohydrate ketogenic diets, have been shown in experiments to delay cancer growth and improve The role of anti-cancer drugs [1-2]
.

But it is a bit difficult for cancer patients to follow these dietary plans.
After all, it is very important for patients to maintain a balanced and adequate nutrition.
The weight loss effect brought by these dietary plans is not beneficial to treatment
.

If we can clarify the mechanism behind how diet helps fight cancer, we will be able to find new anti-cancer ideas more accurately
.

This week, "Nature" magazine published the latest research from the scientific research team of the Massachusetts Institute of Technology and Dana-Farber Cancer Institute
.

Scientists have found that, unlike what we thought before, the inhibition of tumor growth by calorie restriction (CR) is not due to the reduction of blood sugar levels, but due to the lack of lipids, especially unsaturated fatty acids [3]
.

On the one hand, CR limits the source of fatty acids; on the other hand, CR also inhibits the activity of unsaturated fatty acid synthase
.

Eventually it leads to an imbalance in the ratio of saturated fatty acids and unsaturated fatty acids, and inhibits tumor growth
.

In fact, whether it is a calorie restriction diet or a ketogenic diet, previous researchers believe that they mainly suppress tumor growth by lowering blood sugar and insulin levels
.

However, there are three simple nutrients, carbohydrates, fats, and proteins.
Do other metabolites also have a role? The researchers conducted experiments in two mouse models of pancreatic cancer and non-small cell lung cancer
.

The calorie restricted diet (CR) "offens" 40% of calories by reducing carbohydrate intake; the ketogenic diet (KD) has normal calories, but the nutritional composition is 90% fat, 9% protein, and 1% carbohydrate
.

Both of these diets can lower blood sugar
.

Glucose is the basis for the survival of cancer cells, so in theory, limiting glucose should have a certain anti-cancer effect [4]
.

Unexpectedly, only the CR group of the two diets showed the effect of inhibiting tumor growth! It seems that sugar is not the key
.

Both CR and KD can lower blood sugar, but only CR showed the effect of inhibiting tumor growth.
The researchers analyzed a series of other metabolites and found that CR and KD have very different effects on fatty acid levels
.

In KD mice, most fatty acid levels increased, but in CR mice, almost all fatty acid levels decreased
.

So is the lack of fatty acids making cancer cells hungry? The effects of CR and KD on fatty acids are quite different
.

When researchers cultured a variety of cancer cells in a fat-poor medium with very few fatty acids, they found that although their growth has slowed down, they can still grow gradually
.

But interestingly, the researchers found a strange phenomenon, the level of 16:1 monounsaturated fatty acids in the fat-poor medium was significantly increased
.

So researchers immediately thought of an enzyme, stearoyl-CoA desaturase (SCD), which can synthesize 16:0/18:0 saturated fatty acids into 16:1/18:1 monounsaturated fatty acids
.

Sure enough, when drugs were used to inhibit the function of SCD, the cancer cells in the lipid-poor medium could no longer continue to proliferate smoothly, and some cancer cell lines even died soon
.

Subsequent analysis of different fatty acid ratios even showed that the toxicity of inhibiting SCD to cancer cells is likely to be derived from the reduction of monounsaturated fatty acids or the increase of saturated fatty acids
.

In short, it is the imbalance between the ratio of unsaturated fatty acids and saturated fatty acids
.

The researchers also tried to transplant mice with SCD-expressing tumors, and found that this can to some extent combat the anti-cancer effect brought by CR
.

After the activity of SCD increases, the tumor suppressor effect of CR decreases.
The expression of SCD is regulated by insulin signal [5]
.

Now we can almost figure out what is going on-both CR and KD can reduce the activity of SCD by lowering insulin levels.
At the same time, CR can cause cancer cells to lack unsaturated fatty acids.
The combination of the two effects achieves tumor growth.
Restrain
.

Researchers are also trying to find corresponding evidence in two large cohorts of the Nurse Health Study (NHS) and the Health Professional Follow-up Study (HPFS)
.

Among the 1165 pancreatic cancer patients, the low-carbohydrate, high-fat, and high-protein diet was associated with longer survival time, and the correlation was stronger in the plant-based diet
.

There is some truth to think about, vegetable fats contain more unsaturated fatty acids than animal fats [6]
.

I didn't expect that the key to the anti-cancer of the calorie-restricted diet lies in the "fuel shortage"
.

It seems that our knowledge of the human body cannot be taken for granted
.

Reference: [1] de Groot, S.
et al.
Nature Commun.
11, 3083 (2020).
[2] Zahra, A.
et al.
Radiat.
Res.
187, 743–754 (2017).
[3] https:// Nencioni, A.
, Caffa, I.
, Cortellino, S.
& Longo, VD Nature Rev.
Cancer 18, 707–719 ( 2018).
[5] Mauvoisin, D.
& Mounier, C.
Hormonal and nutritional regulation of SCD1 gene expression.
Biochimie 93, 78–86 (2011).
[6] Coulston, AM The role of dietary fats in plant-based diets .
Am.
J.
Clin.
Nutr.
70, 512S–515S (1999).
The author of this article | Dai Siyu