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AMP-activated protein kinase (AMPK) is a ubiquitously expressed and highly conserved multisubstrate serine and threonine kinase. It is often referred to as an energy sensor of the cell, as cellular energy fluctuations lead to its activation. AMPK is a heterotrimeric protein complex consisting of one α-, β-, and γ-subunit. The α-subunit includes the kinase domain, while the β- and γ-subunits are regulatory in function. 

Nicolas O. Jørgensen, Rasmus Kjøbsted, Magnus R. Larsen, Jesper B. Birk, ... Jørgen F.P. Wojtaszewski

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Current Issue

Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease

Yanyong Xu, Yingdong Zhu, Shuwei Hu, Xiaoli Pan, ... Yanqiao Zhang

Objective

Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated.

Methods

Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined.

Results

The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation.

Conclusions

Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD.

 

Hepatocyte miR-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease

Yanyong Xu, Yingdong Zhu, Shuwei Hu, Xiaoli Pan, ... Yanqiao Zhang

Objective

Hepatic miR-34a expression is elevated in diet-induced or genetically obese mice and patients with non-alcoholic steatohepatitis (NASH), yet hepatocyte miR-34a's role in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to NASH remains to be elucidated.

Methods

Mice overexpressing or deficient in hepatocyte miR-34a and control mice were fed a diet enriched in fats, cholesterol, and fructose (HFCF) to induce NASH. C57BL/6 mice with NASH were treated with an miR-34a inhibitor or a scramble control oligo. The effect of miR-34a on the development, progression, and reversal of NAFLD was determined.

Results

The hepatocyte-specific expression of miR-34a aggravated HFCF diet-induced NAFLD. In contrast, germline or adult-onset deletion of hepatocyte miR-34a attenuated the development and progression of NAFLD. In addition, pharmacological inhibition of miR-34a reversed HFCF diet-induced steatohepatitis. Mechanistically, hepatocyte miR-34a regulated the development and progression of NAFLD by inducing lipid absorption, lipogenesis, inflammation, and apoptosis but inhibiting fatty acid oxidation.

Conclusions

Hepatocyte miR-34a is an important regulator in the development and progression of NAFLD. MiR-34a may be a useful target for treating NAFLD.

 

2020 impact factor: 7.4

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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