Mol Cell: Zhu Jian's research group reveals the mechanism of essential amino acids against fatty liver disease

Fatty liver disease is a " wealthy disease " caused by excess nutrition in the eyes of most people
.

In fact, there are also many patients with fatty liver disease who are thin, accounting for 20% of the total number of patients with fatty liver disease [ 1 ]

Fatty liver disease is a " wealthy disease " caused by excess nutrition in the eyes of most people

" When we're lost, fruit flies always point us in the right direction

Schematic diagram of lipid metabolism regulation in humans (left) and Drosophila (right)

Schematic diagram of lipid metabolism regulation in humans (left) and Drosophila (right)

On March 3 , 2022 , a research paper titled "Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination" was published online in Molecular Cell by Prof.

Zhu Jian's research group from Peking University School of Life Sciences and Peking University - Tsinghua Joint Center for Life Sciences .
Using Drosophila larval magenta cells as a research system, they found that insufficient intake of essential amino acids is the " culprit " of fatty liver disease in malnourished people .
When essential amino acids are deficient, the E3 ubiquitin ligase Ubr1 in hepatocytes is inactivated and cannot catalyze the polyubiquitination degradation of the lipid droplet protection protein Plin2 .
Elevated levels of Plin2 protein inhibit the breakdown of liver fat, resulting in fatty liver disease .

On March 3 , 2022 , a research paper titled "Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination" was published online in Molecular Cell by Prof.
Zhu Jian's research group from Peking University School of Life Sciences and Peking University - Tsinghua Joint Center for Life Sciences .
Using Drosophila larval magenta cells as a research system, they found that insufficient intake of essential amino acids is the " culprit " of fatty liver disease in malnourished people .
When essential amino acids are deficient, the E3 ubiquitin ligase Ubr1 in hepatocytes is inactivated and cannot catalyze the polyubiquitination degradation of the lipid droplet protection protein Plin2 .
Elevated levels of Plin2 protein inhibit the breakdown of liver fat, resulting in fatty liver disease .

Screenshot of the paper

Screenshot of the paper

Zhu Jian's group found that Ubr1 is an important essential amino acid receptor in hepatocytes, but unlike known amino acid binding proteins [ 7 ], it can distinguish between essential amino acids and non-essential amino acids
.

Seven essential amino acids (arginine, lysine, histidine, leucine, isoleucine, tryptophan, and phenylalanine) can directly bind and activate Ubr1 , enabling it to catalyze the ubiquitination of its substrate Plin2 .
peptide degradation, thereby alleviating fat accumulation in hepatocytes

Zhu Jian's group found that Ubr1 is an important essential amino acid receptor in hepatocytes, but unlike known amino acid binding proteins [ 7 ], it can distinguish between essential amino acids and non-essential amino acids

Leucine and isoleucine enhance the ability of Drosophila larvae to defend against fat accumulation in purple cells

Leucine and isoleucine enhance the ability of Drosophila larvae to defend against fat accumulation in purple cells

As the chronic liver disease with the highest incidence in the world, fatty liver disease is a serious threat to human life and health
.

Although a lot of human, material and financial resources have been expended, there is still no drug for the treatment of fatty liver disease approved for marketing

As the chronic liver disease with the highest incidence in the world, fatty liver disease is a serious threat to human life and health

Schematic diagram of the molecular mechanism of essential amino acids in improving fatty liver disease 

Schematic diagram of the molecular mechanism of essential amino acids in improving fatty liver disease 

Zhang Yansong, a doctoral student at the School of Life Sciences, Peking University, Lin Siyuan, a doctoral student at the Tsinghua - Peking University Joint Center for Life Sciences, and Peng Jingyu, an undergraduate student at the School of Life Sciences at Peking University are the co-first authors of the paper.

Associate researchers Zhu Jian and Liu Min are the joint correspondents of this paper.
author

Zhang Yansong, a doctoral student at the School of Life Sciences, Peking University, Lin Siyuan, a doctoral student at the Tsinghua - Peking University Joint Center for Life Sciences, and Peng Jingyu, an undergraduate student at the School of Life Sciences at Peking University are the co-first authors of the paper.
Associate researchers Zhu Jian and Liu Min are the joint correspondents of this paper.

references:

1.

1.

2.
Williams, CD (1933).
A nutritional disease of childhood associated with a maize diet.
Arch.
Dis.
Child.
8, 423-433.

3.
Hughes, W.
(1945).
Fatty liver and malignant malnutrition.
The Lancet 246, 861-862.

3.
Hughes, W.
(1945).
Fatty liver and malignant malnutrition.
The Lancet 246, 861-862.

4.
Fontana, L.
, and Partridge, L.
(2015).
Promoting health and longevity through diet: from model organisms to humans.
Cell 161, 106-118.

4.
Fontana, L.
, and Partridge, L.
(2015).
Promoting health and longevity through diet: from model organisms to humans.
Cell 161, 106-118.

5.
Bilder, D.
, Ong, K.
, Hsi, TC, Adiga, K.
, and Kim, J.
(2021).
Tumour-host interactions through the lens of Drosophila.
Nat.
Rev.
Cancer 21, 687-700 .

5.
Bilder, D.
, Ong, K.
, Hsi, TC, Adiga, K.
, and Kim, J.
(2021).
Tumour-host interactions through the lens of Drosophila.
Nat.
Rev.
Cancer 21, 687-700 .

6.
Gutierrez, E.
, Wiggins, D.
, Fielding, B.
, and Gould, AP (2007).
Specialized hepatocyte-like cells regulate Drosophila lipid metabolism.
Nature 445, 275-280.

6.
Gutierrez, E.
, Wiggins, D.
, Fielding, B.
, and Gould, AP (2007).
Specialized hepatocyte-like cells regulate Drosophila lipid metabolism.
Nature 445, 275-280.

7.
Efeyan, A.
, Comb, WC, and Sabatini, DM (2015).
Nutrient-sensing mechanisms and pathways.
Nature 517, 302-310.

7.
Efeyan, A.
, Comb, WC, and Sabatini, DM (2015).
Nutrient-sensing mechanisms and pathways.
Nature 517, 302-310.

 

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