Cell sub-journal: Hormones prevent the development of fatty liver

A team of researchers at the Medical University of Vienna has discovered a regulatory loop controlled by leptin, a hormone derived from fat cells that regulates liver lipid metabolism
through the autonomic nervous system.
This study provides evidence that this adipose tissue-brain-liver axis, previously found in animal models, is also present in humans and opens up new avenues
for the treatment of metabolic diseases such as fatty liver.

Thomas Scherer and Matthöus Metz from the Department of Endocrinology and Metabolism ( Medical University Vienna and the Third Department of Medicine of the Vienna General Hospital ) conducted the study with the aim of determining the effects of leptin on fat metabolism in the human liver , independent of
its anorexia effects.
The adipose tissue hormone leptin circulates in the blood, is related to fat mass, and acts primarily as a satiety signal
in the brain.
In addition to controlling appetite, it is also involved in regulating glycolipid metabolism
.
These effects are mediated through the autonomic nervous system, which connects the brain and surrounding organs such as the liver and adipose tissue
.
Human recombinant leptin (metreleptin) is approved for the treatment of lipodystrophy
.
In these patients with leptin deficiency, the reduction of liver fat levels by metreleptin was not related
to food intake.
So far, however, the underlying mechanism is unclear
.

In previous animal experiments, the team demonstrated that leptin stimulates the liver to release lipids while inhibiting the formation of new lipids, thereby reducing liver fat content
.
This effect relies on the complete autonomic innervation of the liver, which disappears after severing the vagus
nerve.

In the current study, the authors tested whether there is a similar mechanism that regulates liver lipid metabolism
in humans.
They showed that a single injection of metreleptin stimulated liver lipid output in healthy, normal-weight men and reduced liver fat content
.
A similar effect was seen after modified sham eating, a process that induces the cephasic reflex that physiologically stimulates the vagus nerve
.
Conversely, metreleptin does not promote liver lipid secretion in liver transplant recipients whose livers are not innervated
by the autonomic nervous system as a result of transplantation.

Therefore, this study shows that leptin also regulates the fat content of the human liver through the brain and autonomic nervous system, explains study leader Thomas Scherer: "Our results show that, similar to previously observed in animal models, leptin also stimulates the release of lipids in the human liver, thereby reducing liver fat content
through the central nervous system and vagus nerve.
" The researchers therefore hypothesized that leptin could prevent the development of
fatty liver independently of its appetite-suppressing effects.
In addition, the study also showed that the brain has an impact
on liver fat metabolism through the human autonomic nervous system.
This could lead to new treatment options
involving the central nervous system for the prevention of widespread fatty liver disease.